TH9 Cells in Immunity and Disease


T helper (TH) cells differentiated from CD4+ T cells comprise an integral part of the adaptive immune system by providing the ‘help’ for humoral and cellular immune responses. Subsets of TH cells are defined based on the production of signature cytokines that regulate subsequent inflammatory immune responses. Among the TH subsets, TH9 cells are identified by secretion of the signature cytokine IL‐9. Although TH9 cells share some functional roles with TH2 cells, including promoting allergic inflammation and helminthic parasite immunity, TH9 cells can also promote autoimmunity in responses that are generally characterised as dependent on TH1 or TH17 cells. This article offers a concise summary of some key features of TH9 cells and describes how they contribute to immunity and disease.

Key Concepts

  • TH9 cells are differentiated under a cytokine environment containing both IL‐4 and transforming growth factor β (TGFβ), which induce the transcriptional network required for the expression of IL‐9.
  • The TH9 subset is defined by its ability to produce large amounts of the signature cytokine IL‐9.
  • Transcription factors required for the development of TH9 cells include signal transducer and activator of transcription‐6 (STAT6), interferon regulatory factor 4 (IRF4), B‐cell activating transcription factor‐like (BATF), GATA3, PU.1 and Smads.
  • TH9 cells express high levels of IL‐25 receptor (Il17rb), which is a potential surface maker to distinguish TH9 cells from other TH subsets.
  • Immune responses mediated by TH9 cells contribute to the protective immunity against intestinal parasite infection and to antitumour immunity; they are also involved in allergic, inflammatory and autoimmune diseases.

Keywords: IL‐9; TH9; cytokines; transcription factors; parasite infection; allergic reactions; inflammatory diseases; autoimmune diseases

Figure 1. The transcription factors involved in the development of TH9 subset for the production of IL‐9. TH9 cells are differentiated following stimulation with two cytokines IL‐4 and TGFβ, resulting in the activation or induction of transcription factors that promote the expression of Il9. Additional cytokines such as IL‐2, TSLP, IL‐25, IL‐1 and IFNα/β, through activation of their respective transcription factors, can further enhance the expression of Il9 by TH9 cells. Transcription factors that are able to directly bind to the Il9 locus are indicated with arrows.


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Further Reading

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Goswami R and Kaplan MH (2011) A brief history of IL‐9. Journal of Immunology 186: 3283–3288.

Jabeen R and Kaplan MH (2012) The symphony of the ninth: the development and function of Th9 cells. Current Opinion in Immunology 24: 303–307.

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Kaplan MH, Hufford MM and Olson MR (2015) The development and in vivo function of T helper 9 cells. Nature Reviews Immunology 15 (5): 295–307.

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Petermann F and Korn T (2011) Cytokines and effector T cell subsets causing autoimmune CNS disease. FEBS Letters 585: 3747–3757.

Schmitt E, Klein M and Bopp T (2014) Th9 cells, new players in adaptive immunity. Trends in Immunology 35: 61–68.

Soroosh P and Doherty TA (2009) Th9 and allergic disease. Immunology 127: 450–458.

Wilhelm C, Turner JE, Van Snick J and Stockinger B (2012) The many lives of IL‐9: a question of survival? Nature Immunology 13: 637–641.

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Chang, Hua‐Chen, and Kaplan, Mark H(Oct 2015) TH9 Cells in Immunity and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0026234]