Chitinase-3-like 1 regulates TH2 cells, TFHcells and IgE following helminth infection

Abstract

AbstractData from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for the chitinase-like protein ChI3L1 in allergic disease. To address whether CHI3L1 also contributes to TH2 responses following nematode infection, we infectedChi3l1-/-mice withHeligmosomoides polygyrus(Hp) and analyzed T cell responses. Not surprisingly, we observed impaired TH2 responses inHp-infectedChi3l1-/-mice. However, we also found that T cell intrinsic expression ofChi3l1was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4+TFHsubset, which supports germinal center (GC) B cell reactions and IgE responses. The requirement forChi3l1in TFHand IgE responses was also seen following alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection induced IgG1 responses. These results suggest thatChi3l1specifically modulates IgE responses that are highly dependent on help from IL-4-producing TFHcells.