Interleukin-33 promoting Th1 lymphocyte differentiation dependents on IL-12

Mousa Komai-Koma,Eryi Wang,Mariola Kurowska-Stolarska,Dong Li,Charles Mcsharry,Damo Xu

doi:10.1016/j.imbio.2015.11.013

Abstract

The pro-Th2 cytokine IL-33 is now emerging as an important Th1 cytokine-IFN-γ inducer in murine CD4+ T cells that is essential for protective cell-mediated immunity against viral infection in mice. However, whether IL-33 can promote human Th1 cell differentiation and how IL-33 polarizes Th1 cells is less understood. We assessed the ability of IL-33 to induce Th1 cell differentiation and IFN-γ production in vitro and in vivo. We report here that IL-33 alone had no ability in Th1 cell polarization. However it potentiated IL-12-mediated Th1 cell differentiation and IFN-γ production in TCR-stimulated murine and human CD4+ T cells in vitro and in vivo. IL-33 promoted Th1 cell development via MyD88 and synergized with IL-12 to enhance St2 and IL-12R expression in CD4+ T cells.These data therefore provide a novel mechanism for Th1 cell differentiation and optimal induction of a Type 1 response. Thus, IL-33 is capable of inducing IL-12-dependent Th1 cell differentiation in human and mouse CD4+ T cells.

Highlights

The recognition that CD4+ T cells can be differentiated into functionally distinct subsets, including Th1 and Th2 cells, based on their distinct profile of cytokines to which they respond and secrete after stimulation, represented a major advance in immunology (Mosmann and Coffman, 1989; Sher and Coffman, 1992)
Data reported in this study reveal a hitherto unrecognized effect and mechanism by which IL-33, a pro-Th2 cytokine, promotes Th1 cell development in human and in mice
We found that the enhanced ST2 expression induced by IL-33 and IL-12 was down-regulated 72 h after Th1 polarization in vitro

Summary

Introduction

The recognition that CD4+ T cells can be differentiated into functionally distinct subsets, including Th1 and Th2 cells, based on their distinct profile of cytokines to which they respond and secrete after stimulation, represented a major advance in immunology (Mosmann and Coffman, 1989; Sher and Coffman, 1992). IL-4 induces the differentiation of Th2 cells which produce mainly IL-4 and are associated with eradication of extracellular parasites and mediate allergic inflammation Th1 and Th2 cells counter-regulate each other’s function by the relative concentration of the cytokines they produce. The balance of the Th1 and Th2 response frequently determines the outcome of several important infectious and autoimmune diseases (Seder et al, 1993; Constant and Bottomly, 1997; O’Garra et al, 1997). The members of the IL-1 family including IL-1␤ and IL-18 are closely associated with Th1 and Th2 cell differentiation (Xu et al 1998a,b, 2000; Guo et al, 2009); we investigated the role of IL-33 (Schmitz et al, 2005), a member of the IL-1 cytokine family, in the induction and regulation of Th1 cell development in vitro and in vivo

Methods

Results

Conclusion