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Front Immunol. 2019 Mar 20;10:522. doi: 10.3389/fimmu.2019.00522. eCollection 2019.

Pleiotropic Effects of IL-33 on CD4+ T Cell Differentiation and Effector Functions.

Alvarez F1,2,3, Fritz JH1,3,4, Piccirillo CA1,2,3,4.

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Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
Program in Infectious Diseases and Immunology in Global Health, Centre for Translational Biology, The Research Institute of the McGill University Health Center, Montréal, QC, Canada.
Centre of Excellence in Translational Immunology, Montréal, QC, Canada.
McGill University Research Center on Complex Traits, McGill University, Montréal, QC, Canada.


IL-33, a member of the IL-1 family of cytokines, was originally described in 2005 as a promoter of type 2 immune responses. However, recent evidence reveals a more complex picture. This cytokine is released locally as an alarmin upon cellular damage where innate cell types respond to IL-33 by modulating their differentiation and influencing the polarizing signals they provide to T cells at the time of antigen presentation. Moreover, the prominent expression of the IL-33 receptor, ST2, on GATA3+ T helper 2 cells (TH2) demonstrated that IL-33 could have a direct impact on T cells. Recent observations reveal that T-bet+ TH1 cells and Foxp3+ regulatory T (TREG) cells can also express the ST2 receptor, either transiently or permanently. As such, IL-33 can have a direct effect on the dynamics of T cell populations. As IL-33 release was shown to play both an inflammatory and a suppressive role, understanding the complex effect of this cytokine on T cell homeostasis is paramount. In this review, we will focus on the factors that modulate ST2 expression on T cells, the effect of IL-33 on helper T cell responses and the role of IL-33 on TREG cell function.


IL-33; ST2; T cell differentiation; Th17 and Tregs cells; immunoregulation; infection; th1/th2 balance

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