Chitinase-3-like 1 regulates T(H)2 cells, T(FH) cells and IgE responses to helminth infection

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(H)2 responses following nematode infection, we infected Chi3l1 (-/-) mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses. RESULTS: As anticipated, we observed impaired T(H)2 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.