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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.

Author information

1
Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.
2
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.
3
Centre of Excellence in Translational Immunology, Montréal, QC, Canada.
4
McGill University Research Center on Complex Traits, McGill University, Montréal, QC, Canada.

Abstract

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.

KEYWORDS:

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

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