Chitinase-3-like 1 regulates TH2 cells, TFH cells and IgE responses to helminth infection

Abstract

Introduction: Data from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for chitinase-3-like-1 protein (CHI3L1) in allergic disease.

Methods: To address whether Chi3l1 also contributes to T_H2 responses following nematode infection, we infected Chi3l1 ^-/- mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses.

Results: As anticipated, we observed impaired T_H2 responses in Hp-infected Chi3l1 ^-/- mice. However, we also found that T cell intrinsic expression of Chi3l1 was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4⁺ T_FH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in T_FH, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses.

Discussion: These results suggest that Chi3l1 modulates IgE responses, which are known to be highly dependent on IL-4-producing T_FH cells.

Keywords: IL-4; IgE (immunoglobulin E); T follicular helper (T cell FH; T helper 2 (Th2) cells; enteric; germinal center; germinal center (GC) B cells; helminth.