Skin: Immunological Defence Mechanisms


Human skin is the largest organ of the body providing a protective coat to ensure that exogenous ‘noxious’ agents do not jeopardise the function of vital internal organ systems. Being situated at the interface between external and internal milieus, a number of remarkable structural and functional characteristics of skin have been delineated that contribute to its effectiveness at maintaining homoeostasis. For instance, skin is normally healthy despite the fact that it is regularly colonised by a variety of organisms. Antimicrobial peptides secreted by skin cells contribute to this homoeostatic maintenance of microorganisms by forming a shield against infectious agents. Several immune cell types are also resident in the skin and are ready to respond to a variety of stimuli. Balancing the multiple skin defensive mechanisms is important for achieving homoeostasis as disruption of any of these components contribute to the manifestation of skin diseases.

Key Concepts:

  • Normal skin consists of multiple cell types – some that form the different layers and others that function as sentinels of the immune system.

  • Skin is colonised by a variety of microorganisms under homoeostatic conditions.

  • Skin has multiple innate defence mechanisms that are disrupted during dermatological diseases.

  • Adaptive immunity in the skin is shaped by the response of different dendritic cells and T‐cells that are ready to respond to different stimuli.

  • AMPs are natural antibiotics that are present in the skin to prevent overgrowth of microorganisms.

  • Dysregulated production of AMPs is associated with a variety of dermatological diseases.

Keywords: adhesion molecules; apoptosis; corticosteroids; cyclosporin A; cytokines; hypersensitivity reaction; irritants; interleukin; kaposi sarcoma; keratinocytes; langerhans cells; melanocytes; skin cancer; T lymphocyte; ultraviolet light; urushiol

Figure 1.

Normal human skin includes a keratinised stratified squamous epidermis (stratum corneum, stratum granulosum, stratum spinosum and basal cell layer) including keratinocytes and a variety of immune cells. Immune cells are dispersed in both the epidermis and the dermis. Different populations predominate in the dermis compared with the epidermis.

Figure 2.

(a) Patient presented with itching and scaling on the ear associated with wearing costume jewellery. (b) Subsequent diagnostic patch testing revealed a strong reaction to Ni (right) but not other allergens (left). (c) A representative H&E‐stained section of allergic contact dermatitis lesion biopsy shows spongiotic dermatitis with lymphocytic infiltration and exocytosis of lymphocytes into the epidermis. (d) Overview of molecular and cellular events in allergic contact dermatitis highlighting an allergen such as nickel (red triangles) penetrating into the epidermis surface, captured by epidermal (LC) and dermal DC, which migrate to local lymph nodes, educating conventional T‐lymphocytes. On rechallenge with a specific allergen, memory/effector T‐lymphocytes migrate into the skin (dermis and epidermis), mediating tissue damage.



Acharya MR, Venitz J, Figg WD and Sparreboom A (2004) Chemically modified tetracyclines as inhibitors of matrix metalloproteinases. Drug Resistance Updates 7(3): 195–208.

Agerberth B, Gunne H, Odeberg J et al. (1995) FALL‐39, a putative human peptide antibiotic, is cysteine‐free and expressed in bone marrow and testis. Proceedings of the National Academy of Sciences of the USA 92(1): 195–199.

Ahmadzadeh M, Felipe‐Silva A, Heemskerk B et al. (2008) FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions. Blood 112(13): 4953–4960.

Ali RS, Falconer A, Ikram M et al. (2001) Expression of the peptide antibiotics human beta defensin‐1 and human beta defensin‐2 in normal human skin. Journal of Investigative Dermatology 117(1): 106–111.

Aliahmadi E, Gramlich R, Grutzkau A et al. (2009) TLR2‐activated human langerhans cells promote Th17 polarization via IL‐1beta, TGF‐beta and IL‐23. European Journal of Immunology 39(5): 1221–1230.

Allan RS, Smith CM, Belz GT et al. (2003) Epidermal viral immunity induced by CD8alpha+ dendritic cells but not by Langerhans cells. Science 301(5641): 1925–1928.

Andl T, Murchison EP, Liu F et al. (2006) The miRNA‐processing enzyme dicer is essential for the morphogenesis and maintenance of hair follicles. Current Biology 16(10): 1041–1049.

Bals R and Wilson JM (2003) Cathelicidins – a family of multifunctional antimicrobial peptides. Cellular and Molecular Life Sciences 60(4): 711–720.

Bangert C, Brunner PM and Stingl G (2011) Immune functions of the skin. Clinics in Dermatology 29(4): 360–376.

Barker JN, Mitra RS , Griffiths CE, Dixit VM and Nickoloff BJ (1991) Keratinocytes as initiators of inflammation. Lancet 337(8735): 211–214.

Bedoui S, Whitney PG, Waithman J et al. (2009) Cross‐presentation of viral and self antigens by skin‐derived CD103+ dendritic cells. Nature Immunology 10(5): 488–495.

Bergstresser PR, Sullivan S, Streilein JW and Tigelaar RE (1985) Origin and function of Thy‐1+ dendritic epidermal cells in mice. Journal of Investigative Dermatology 85(suppl. 1): 85s–90s.

Bos JD, de Boer OJ, Tibosch E, Das PK and Pals ST (1993) Skin‐homing T lymphocytes: detection of cutaneous lymphocyte‐associated antigen (CLA) by HECA‐452 in normal human skin. Archives of Dermatological Research 285(4): 179–183.

Bos JD, de Rie MA, Teunissen MB and Piskin G (2005) Psoriasis: dysregulation of innate immunity. British Journal of Dermatology 152(6): 1098–1107.

Bos JD, Hagenaars C, Das PK et al. (1989) Predominance of “memory” T cells (CD4+, CDw29+) over “naive” T cells (CD4+, CD45R+) in both normal and diseased human skin. Archives of Dermatological Research 281(1): 24–30.

Bos JD and Kapsenberg ML (1993) The skin immune system: progress in cutaneous biology. Immunology Today 14(2): 75–78.

Boyman O, Hefti HP, Conrad C et al. (2004) Spontaneous development of psoriasis in a new animal model shows an essential role for resident T cells and tumor necrosis factor‐alpha. Journal of Experimental Medicine 199(5): 731–736.

Bursch LS, Wang L, Igyarto B et al. (2007) Identification of a novel population of Langerin+ dendritic cells. Journal of Experimental Medicine 204(13): 3147–3156.

Cai Y, Shen X, Ding C et al. (2011) Pivotal role of dermal IL‐17‐producing gammadelta T cells in skin inflammation. Immunity 35(4): 596–610.

Campbell JJ, Haraldsen G, Pan J et al. (1999) The chemokine receptor CCR4 in vascular recognition by cutaneous but not intestinal memory T cells. Nature 400(6746): 776–780.

Clark RA (2010) Skin‐resident T cells: the ups and downs of on site immunity. Journal of Investigative Dermatology 130(2): 362–370.

Clark RA, Chong B, Mirchandani N et al. (2006) The vast majority of CLA+ T cells are resident in normal skin. Journal of Immunology 176(7): 4431–4439.

Clark RA, Huang SJ, Murphy GF et al. (2008) Human squamous cell carcinomas evade the immune response by down‐regulation of vascular E‐selectin and recruitment of regulatory T cells. Journal of Experimental Medicine 205(10): 2221–2234.

Cooper K (1976) Immunity mechanisms. In: Lofts B (ed.) Physiology of the Amphibian, pp. 164–179. New York: Academic Press.

Cunningham AL, Carbone F and Geijtenbeek TB (2008) Langerhans cells and viral immunity. European Journal of Immunology 38(9): 2377–2385.

Di Nardo A, Vitiello A and Gallo RL (2003) Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. Journal of Immunology 170(5): 2274–2278.

Dombrowski Y, Peric M, Koglin S et al. (2011) Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Science Translational Medicine 3(82): 82ra38.

Ebner S, Ehammer Z, Holzmann S et al. (2004) Expression of C‐type lectin receptors by subsets of dendritic cells in human skin. International Immunology 16(6): 877–887.

Elbe A, Foster CA and Stingl G (1996) T‐cell receptor alpha beta and gamma delta T cells in rat and human skin – are they equivalent? Seminars in Immunology 8(6): 341–349.

Elias PM and Friend DS (1975) The permeability barrier in mammalian epidermis. Journal of Cell Biology 65(1): 180–191.

Elias PM and Menon GK (1991) Structural and lipid biochemical correlates of the epidermal permeability barrier. Advances in Lipid Research 24: 1–26.

Eyerich S, Onken AT, Weidinger S et al. (2011) Mutual antagonism of T cells causing psoriasis and atopic eczema. New England Journal of Medicine 365(3): 231–238.

Fontenot JD, Gavin MA and Rudensky AY (2003) Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunology 4(4): 330–336.

Foster CA, Yokozeki H, Rappersberger K et al. (1990) Human epidermal T cells predominantly belong to the lineage expressing alpha/beta T cell receptor. Journal of Experimental Medicine 171(4): 997–1013.

Frohm M, Agerberth B, Ahangari G et al. (1997) The expression of the gene coding for the antibacterial peptide LL‐37 is induced in human keratinocytes during inflammatory disorders. Journal of Biological Chemistry 272(24): 15258–15263.

Fujita M, Miyachi Y, Nakata K and Imamura S (1993) gamma delta T‐cell receptor‐positive cells of human skin. II. Appearance in delayed‐type hypersensitivity reaction. Archives of Dermatological Research 285(7): 436–440.

Fulton C, Anderson GM, Zasloff M, Bull R and Quinn AG (1997) Expression of natural peptide antibiotics in human skin. Lancet 350(9093): 1750–1751.

Gallo RL and Hooper LV (2012) Epithelial antimicrobial defence of the skin and intestine. Nature Reviews Immunology 12(7): 503–516.

Gallo RL and Nakatsuji T (2011) Microbial symbiosis with the innate immune defense system of the skin. Journal of Investigative Dermatology 131(10): 1974–1980.

Gallo RL, Ono M, Povsic T et al. (1994) Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline‐rich antimicrobial peptide from wounds. Proceedings of the National Academy of Sciences of the USA 91(23): 11035–11039.

Ganguly D, Chamilos G, Lande R et al. (2009) Self‐RNA‐antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8. Journal of Experimental Medicine 206(9): 1983–1994.

Gell PGH, Coombs RRA and Lachmann P (1974) Clinical Aspects of Immunology. Oxford: Blackwell Science Publications Ltd.

Ginhoux F, Collin MP, Bogunovic M et al. (2007) Blood‐derived dermal langerin+ dendritic cells survey the skin in the steady state. Journal of Experimental Medicine 204(13): 3133–3146.

Girardi M, Oppenheim DE, Steele CR et al. (2001) Regulation of cutaneous malignancy by gammadelta T cells. Science 294(5542): 605–609.

Girardi M, Lewis JM, Filler RB, Hayday AC and Tigelaar RE (2006) Environmentally responsive and reversible regulation of epidermal barrier function by gammadelta T cells. Journal of Investigative Dermatology 126(4): 808–814.

Glaser R, Harder J, Lange H et al. (2005) Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection. Nature Immunology 6(1): 57–64.

Glaser R, Meyer‐Hoffert U, Harder J et al. (2009) The antimicrobial protein psoriasin (S100A7) is upregulated in atopic dermatitis and after experimental skin barrier disruption. Journal of Investigative Dermatology 129(3): 641–649.

Gober MD, Fishelevich R, Zhao Y, Unutmaz D and Gaspari AA (2008) Human natural killer T cells infiltrate into the skin at elicitation sites of allergic contact dermatitis. Journal of Investigative Dermatology 128(6): 1460–1469.

Gomez de Aguero M, Vocanson M, Hacini‐Rachinel F et al. (2012) Langerhans cells protect from allergic contact dermatitis in mice by tolerizing CD8(+) T cells and activating Foxp3(+) regulatory T cells. Journal of Clinical Investigation 122(5): 1700–1711.

Gottlieb AB, Chamian F, Masud S et al. (2005) TNF inhibition rapidly down‐regulates multiple proinflammatory pathways in psoriasis plaques. Journal of Immunology 175(4): 2721–2729.

Gray EE, Suzuki K and Cyster JG (2011) Cutting edge: Identification of a motile IL‐17‐producing gammadelta T cell population in the dermis. Journal of Immunology 186(11): 6091–6095.

Gregorio J, Meller S, Conrad C et al. (2010) Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. Journal of Experimental Medicine 207(13): 2921–2930.

Grice EA and Segre JA (2011) The skin microbiome. Nature Reviews Microbiology 9(4): 244–253.

Griffiths CE, Strober BE, van de Kerkhof P et al. (2010) Comparison of ustekinumab and etanercept for moderate‐to‐severe psoriasis. New England Journal of Medicine 362(2): 118–128.

Gudmundsson GH, Agerberth B, Odeberg J et al. (1996) The human gene FALL39 and processing of the cathelin precursor to the antibacterial peptide LL‐37 in granulocytes. European Journal of Biochemistry 238(2): 325–332.

Guilliams M, Crozat K, Henri S et al. (2010) Skin‐draining lymph nodes contain dermis‐derived CD103(‐) dendritic cells that constitutively produce retinoic acid and induce Foxp3(+) regulatory T cells. Blood 115(10): 1958–1968.

Gutierrez‐Steil C, Wrone‐Smith T, Sun X et al. (1998) Sunlight‐induced basal cell carcinoma tumor cells and ultraviolet‐B‐irradiated psoriatic plaques express Fas ligand (CD95L). Journal of Clinical Investigation 101(1): 33–39.

Haake AR and Polakowska RR (1993) Cell death by apoptosis in epidermal biology. Journal of Investigative Dermatology 101(2): 107–112.

Hanifin JM and Rogge JL (1977) Staphylococcal infections in patients with atopic dermatitis. Archives of Dermatology 113(10): 1383–1386.

Harder J and Schroder JM (2005) Psoriatic scales: a promising source for the isolation of human skin‐derived antimicrobial proteins. Journal of Leukocyte Biology 77(4): 476–486.

Harder J, Bartels J, Christophers E and Schroder JM (1997) A peptide antibiotic from human skin. Nature 387(6636): 861.

Harder J, Bartels J, Christophers E and Schroder JM (2001) Isolation and characterization of human beta‐defensin‐3, a novel human inducible peptide antibiotic. Journal of Biological Chemistry 276(8): 5707–5713.

Henri S, Poulin LF, Tamoutounour S et al. (2010) CD207+ CD103+ dermal dendritic cells cross‐present keratinocyte‐derived antigens irrespective of the presence of Langerhans cells. Journal of Experimental Medicine 207(1): 189–206.

Hollox EJ, Huffmeier U, Zeeuwen PL et al. (2008) Psoriasis is associated with increased beta‐defensin genomic copy number. Nature Genetics 40(1): 23–25.

Holtmeier W, Pfander M, Hennemann A et al. (2001) The TCR‐delta repertoire in normal human skin is restricted and distinct from the TCR‐delta repertoire in the peripheral blood. Journal of Investigative Dermatology 116(2): 275–280.

Human Microbiome Project Consortium (2012) Structure, function and diversity of the healthy human microbiome. Nature 486(7402): 207–214.

Igyarto BZ, Haley K, Ortner D et al. (2011) Skin‐resident murine dendritic cell subsets promote distinct and opposing antigen‐specific T helper cell responses. Immunity 35(2): 260–272.

de Jongh GJ, Zeeuwen PL, Kucharekova M et al. (2005) High expression levels of keratinocyte antimicrobial proteins in psoriasis compared with atopic dermatitis. Journal of Investigative Dermatology 125(6): 1163–1173.

Kagan BL, Selsted ME, Ganz T and Lehrer RI (1990) Antimicrobial defensin peptides form voltage‐dependent ion‐permeable channels in planar lipid bilayer membranes. Proceedings of the National Academy of Sciences of the USA 87(1): 210–214.

Kaplan DH (2010) In vivo function of Langerhans cells and dermal dendritic cells. Trends in Immunology 31(12): 446–451.

Kaplan DH, Kissenpfennig A and Clausen BE (2008) Insights into Langerhans cell function from Langerhans cell ablation models. European Journal of Immunology 38(9): 2369–2376.

Kaplan DH, Jenison MC, Saeland S, Shlomchik WD and Shlomchik MJ (2005) Epidermal langerhans cell‐deficient mice develop enhanced contact hypersensitivity. Immunity 23(6): 611–620.

Kaporis HG, Guttman‐Yassky E, Lowes MA et al. (2007) Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant microenvironment. Journal of Investigative Dermatology 127(10): 2391–2398.

Kautz‐Neu K, Noordegraaf M, Dinges S et al. (2011) Langerhans cells are negative regulators of the anti‐Leishmania response. Journal of Experimental Medicine 208(5): 885–891.

Kim J, Ochoa MT, Krutzik SR et al. (2002) Activation of toll‐like receptor 2 in acne triggers inflammatory cytokine responses. Journal of Immunology 169(3): 1535–1541.

Kissenpfennig A, Henri S, Dubois B et al. (2005) Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22(5): 643–654.

Kupper TS and Fuhlbrigge RC (2004) Immune surveillance in the skin: mechanisms and clinical consequences. Nature Reviews Immunology 4(3): 211–222.

Lande R, Gregorio J, Facchinetti V et al. (2007) Plasmacytoid dendritic cells sense self‐DNA coupled with antimicrobial peptide. Nature 449(7162): 564–569.

Lee KC and Eckert RL (2007) S100A7 (Psoriasin) – mechanism of antibacterial action in wounds. Journal of Investigative Dermatology 127(4): 945–957.

Lee PH, Ohtake T, Zaiou M et al. (2005) Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection. Proceedings of the National Academy of Sciences of the USA 102(10): 3750–3755.

Liao YH, Jee SH, Sheu BC et al. (2006) Increased expression of the natural killer cell inhibitory receptor CD94/NKG2A and CD158b on circulating and lesional T cells in patients with chronic plaque psoriasis. British Journal of Dermatology 155(2): 318–324.

Lippens S, Denecker G, Ovaere P, Vandenabeele P and Declercq W (2005) Death penalty for keratinocytes: apoptosis versus cornification. Cell Death and Differentiation 12(suppl. 2): 1497–1508.

Mathers AR, Janelsins BM, Rubin JP et al. (2009) Differential capability of human cutaneous dendritic cell subsets to initiate Th17 responses. Journal of Immunology 182(2): 921–933.

Mc Dermott R, Ziylan U, Spehner D et al. (2002) Birbeck granules are subdomains of endosomal recycling compartment in human epidermal Langerhans cells, which form where Langerin accumulates. Molecular Biology of the Cell 13(1): 317–335.

Merad M, Ginhoux F and Collin M (2008) Origin, homeostasis and function of Langerhans cells and other langerin‐expressing dendritic cells. Nature Reviews Immunology 8(12): 935–947.

Merad M, Manz MG, Karsunky H et al. (2002) Langerhans cells renew in the skin throughout life under steady‐state conditions. Nature Immunology 3(12): 1135–1141.

Muller HK, Bucana C and Kripke ML (1992) Antigen presentation in the skin: modulation by u.v. radiation and chemical carcinogens. Seminars in Immunology 4(4): 205–215.

Murakami M, Ohtake T, Dorschner RA et al. (2002) Cathelicidin anti‐microbial peptide expression in sweat, an innate defense system for the skin. Journal of Investigative Dermatology 119(5): 1090–1095.

Murphy G (1991) The secret of NIN: a novel neural‐immunological network potentially integral to immunological function in human skin. In: Nickoloff BJ (ed.) Dermal Immune System, 227–244. Boca Raton, Florida: CRC Press.

Nagao K, Ginhoux F, Leitner WW et al. (2009) Murine epidermal Langerhans cells and langerin‐expressing dermal dendritic cells are unrelated and exhibit distinct functions. Proceedings of the National Academy of Sciences of the USA 106(9): 3312–3317.

Nagy I, Pivarcsi A, Kis K et al. (2006) Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes and Infection 8(8): 2195–2205.

Nestle FO, Di Meglio P, Qin Z and Nickoloff BJ (2009b) Skin immune sentinels in health and disease. Nature Reviews Immunology 9(10): 679–691.

Nestle FO, Kaplan DH and Barker J (2009a) Psoriasis. New England Journal of Medicine 361(5): 496–509.

Nickoloff BJ (2006) Keratinocytes regain momentum as instigators of cutaneous inflammation. Trends in Molecular Medicine 12(3): 102–106.

Nickoloff BJ and Naidu Y (1994) Perturbation of epidermal barrier function correlates with initiation of cytokine cascade in human skin. Journal of the American Academy of Dermatology 30(4): 535–546.

Nickoloff BJ and Nestle FO (2004) Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. Journal of Clinical Investigation 113(12): 1664–1675.

Nomura I, Goleva E, Howell MD et al. (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. Journal of Immunology 171(6): 3262–3269.

Ong PY, Ohtake T, Brandt C et al. (2002) Endogenous antimicrobial peptides and skin infections in atopic dermatitis. New England Journal of Medicine 347(15): 1151–1160.

Paus R, Nickoloff BJ and Ito T (2005) A ‘hairy’ privilege. Trends in Immunology 26(1): 32–40.

Paus R, van der Veen C, Eichmuller S et al. (1998) Generation and cyclic remodeling of the hair follicle immune system in mice. Journal of Investigative Dermatology 111(1): 7–18.

Payne AS, Hanakawa Y, Amagai M and Stanley JR (2004) Desmosomes and disease: pemphigus and bullous impetigo. Current Opinion in Cell Biology 16(5): 536–543.

Peric M, Lehmann B, Vashina G et al. (2010) UV‐B‐triggered induction of vitamin D3 metabolism differentially affects antimicrobial peptide expression in keratinocytes. Journal of Allergy and Clinical Immunology 125(3): 746–749.

Poulin LF, Henri S, de Bovis B et al. (2007) The dermis contains langerin+ dendritic cells that develop and function independently of epidermal Langerhans cells. Journal of Experimental Medicine 204(13): 3119–3131.

Raj D, Brash DE and Grossman D (2006) Keratinocyte apoptosis in epidermal development and disease. Journal of Investigative Dermatology 126(2): 243–257.

Rieg S, Steffen H, Seeber S et al. (2005) Deficiency of dermcidin‐derived antimicrobial peptides in sweat of patients with atopic dermatitis correlates with an impaired innate defense of human skin in vivo. Journal of Immunology 174(12): 8003–8010.

Romani N, Brunner PM and Stingl G (2012) Changing views of the role of Langerhans cells. Journal of Investigative Dermatology 132(3 Pt 2): 872–881.

Romani N, Clausen BE and Stoitzner P (2010) Langerhans cells and more: langerin‐expressing dendritic cell subsets in the skin. Immunological Reviews 234(1): 120–141.

Rudensky AY (2011) Regulatory T cells and Foxp3. Immunological Reviews 241(1): 260–268.

Sakaguchi S, Miyara M, Costantino CM and Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nature Reviews Immunology 10(7): 490–500.

Schittek B, Hipfel R, Sauer B et al. (2001) Dermcidin: a novel human antibiotic peptide secreted by sweat glands. Nature Immunology 2(12): 1133–1137.

Schroder JM (1995) Inflammatory mediators and chemoattractants. Clinics in Dermatology 13(2): 137–150.

Schroder JM and Harder J (2006) Antimicrobial skin peptides and proteins. Cellular and Molecular Life Sciences 63(4): 469–486.

Schuler G and Steinman RM (1985) Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. Journal of Experimental Medicine 161(3): 526–546.

Schwarz A, Noordegraaf M, Maeda A et al. (2010) Langerhans cells are required for UVR‐induced immunosuppression. Journal of Investigative Dermatology 130(5): 1419–1427.

Seneschal J, Clark RA, Gehad A, Baecher‐Allan CM and Kupper TS (2012) Human epidermal Langerhans cells maintain immune homeostasis in skin by activating skin resident regulatory T cells. Immunity 36(5): 873–884.

Shklovskaya E, O'Sullivan BJ, Ng LG et al. (2011) Langerhans cells are precommitted to immune tolerance induction. Proceedings of the National Academy of Sciences of the USA 108(44): 18049–18054.

Sigal LJ, Crotty S, Andino R and Rock KL (1999) Cytotoxic T‐cell immunity to virus‐infected non‐haematopoietic cells requires presentation of exogenous antigen. Nature 398(6722): 77–80.

Smith FJ, Irvine AD, Terron‐Kwiatkowski A et al. (2006) Loss‐of‐function mutations in the gene encoding filaggrin cause ichthyosis vulgaris. Nature Genetics 38(3): 337–342.

Sontheimer RD and Tharp MD (1991) Immunological repertoire of the dermal microvascular unit. In: Nickoloff BJ (ed.) Dermal Immune System, pp. 117–148. Boca Raton, Florida: CRC Press.

Sorensen OE, Follin P, Johnsen AH et al. (2001) Human cathelicidin, hCAP‐18, is processed to the antimicrobial peptide LL‐37 by extracellular cleavage with proteinase 3. Blood 97(12): 3951–3959.

Sorensen OE, Thapa DR, Rosenthal A et al. (2005) Differential regulation of beta‐defensin expression in human skin by microbial stimuli. Journal of Immunology 174(8): 4870–4879.

Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annual Review of Immunology 30: 1–22.

Steinman RM and Cohn ZA (1973) Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. Journal of Experimental Medicine 137(5): 1142–1162.

Steinman RM and Cohn ZA (1974) Identification of a novel cell type in peripheral lymphoid organs of mice. II. Functional properties in vitro. Journal of Experimental Medicine 139(2): 380–397.

Stoitzner P, Tripp CH, Eberhart A et al. (2006) Langerhans cells cross‐present antigen derived from skin. Proceedings of the National Academy of Sciences of the USA 103(20): 7783–7788.

Streilein JW (1978) Lymphocyte traffic, T‐cell malignancies and the skin. Journal of Investigative Dermatology 71(3): 167–171.

Sugiyama H, Gyulai R, Toichi E et al. (2005) Dysfunctional blood and target tissue CD4+CD25high regulatory T cells in psoriasis: mechanism underlying unrestrained pathogenic effector T cell proliferation. Journal of Immunology 174(1): 164–173.

Tigelaar RE, Lewis JM and Bergstresser PR (1990) TCR gamma/delta+ dendritic epidermal T cells as constituents of skin‐associated lymphoid tissue. Journal of Investigative Dermatology 94(suppl. 6): 58S–63S.

Toulon A, Breton L, Taylor KR et al. (2009) A role for human skin‐resident T cells in wound healing. Journal of Experimental Medicine 206(4): 743–750.

Ullrich SE (2005) Mechanisms underlying UV‐induced immune suppression. Mutation Research 571(1–2): 185–205.

Vahavihu K, Ala‐Houhala M, Peric M et al. (2010) Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis. British Journal of Dermatology 163(2): 321–328.

Valladeau J, Clair‐Moninot V, Dezutter‐Dambuyant C et al. (2002) Identification of mouse langerin/CD207 in Langerhans cells and some dendritic cells of lymphoid tissues. Journal of Immunology 168(2): 782–792.

Valladeau J, Ravel O, Dezutter‐Dambuyant C et al. (2000) Langerin, a novel C‐type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity 12(1): 71–81.

Wakim LM, Gebhardt T, Heath WR and Carbone FR (2008b) Cutting edge: local recall responses by memory T cells newly recruited to peripheral nonlymphoid tissues. Journal of Immunology 181(9): 5837–5841.

Wakim LM, Waithman J, van Rooijen N, Heath WR and Carbone FR (2008a) Dendritic cell‐induced memory T cell activation in nonlymphoid tissues. Science 319(5860): 198–202.

Wang Z, Lai Y, Bernard JJ et al. (2012) Skin mast cells protect mice against vaccinia virus by triggering mast cell receptor S1PR2 and releasing antimicrobial peptides. Journal of Immunology 188(1): 345–357.

Wollenberg A, Wagner M, Gunther S et al. (2002) Plasmacytoid dendritic cells: a new cutaneous dendritic cell subset with distinct role in inflammatory skin diseases. Journal of Investigative Dermatology 119(5): 1096–1102.

Yadava P, Zhang CC, Sun J and Hughes JA (2006) Antimicrobial activities of human beta‐defensins against Bacillus species. International Journal of Antimicrobial Agents 28(2): 132–137.

Yamasaki K, Di Nardo A, Bardan A et al. (2007) Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea. Nature Medicine 13(8): 975–980.

Yang D, Chen Q, Chertov O and Oppenheim JJ (2000) Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells. Journal of Leukocyte Biology 68(1): 9–14.

Yang D, Chertov O, Bykovskaia SN et al. (1999) Beta‐defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 286(5439): 525–528.

Yi R, O'Carroll D, Pasolli HA et al. (2006) Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nature Genetics 38(3): 356–362.

Zaba LC, Cardinale I, Gilleaudeau P et al. (2007a) Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. Journal of Experimental Medicine 204(13): 3183–3194.

Zaba LC, Fuentes‐Duculan J, Steinman RM, Krueger JG and Lowes MA (2007b) Normal human dermis contains distinct populations of CD11c+BDCA‐1+ dendritic cells and CD163+FXIIIA+ macrophages. Journal of Clinical Investigation 117(9): 2517–2525.

Zaba LC, Fuentes‐Duculan J, Eungdamrong NJ et al. (2009a) Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell‐polarizing myeloid dendritic cells. Journal of Investigative Dermatology 129(1): 79–88.

Zaba LC, Krueger JG and Lowes MA (2009b) Resident and “inflammatory” dendritic cells in human skin. Journal of Investigative Dermatology 129(2): 302–308.

Further Reading

Bos JD (1997) Skin Immune System, 2nd edn. Boca Raton, Florida: CRC Press.

Burg G and Dummer RG (1997) Strategies for Immunointerventions in Dermatology. New York: Springer.

Kalish RS and Johnson KC (1990) Enrichment and function of urushiol (poison ivy) specific T lymphocytes in lesions of allergic contact dermatitis to urushiol. Journal of Immunology 145: 3706–3713.

Koch AE and Strieter RM (1996) Chemokines in Disease. New York: Springer.

Leigh IM, Lane EB and Weh FM (1994) The Keratinocyte Handbook. New York: Cambridge University Press.

Nickoloff BJ (1991) Cytokine network in psoriasis. Archives of Dermatology 127: 871–884.

Nickoloff BJ (1993) Dermal Immune System. Boca Raton, Florida: CRC Press.

Norris DA (1989) Immune Mechanisms in Cutaneous Disease. New York: Marcel Dekker.

Streilein JW, Taylor J, Vincek V et al. (1994) Immune surveillance and sunlight‐induced skin cancer. Immunology Today 15: 174–179.

Thompson CB (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267: 1456–1461.

Valdimarsson H, Baker BS, Jonsdottir I, Powles A and Fox L (1995) Psoriasis: a T‐cell‐mediated autoimmune disease induced by streptococcal superantigens? Immunology Today 16: 145–153.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Shiu, Jessica, Harberts, Erin, Gaspari, Anthony A, and Nickoloff, Brian J(Apr 2013) Skin: Immunological Defence Mechanisms. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001215.pub3]