AUTHOR=Curtiss Miranda L. , Rosenberg Alexander F. , Scharer Christopher D. , Mousseau Betty , Benavides Natalia A. Ballesteros , Bradley John E. , León Beatriz , Steele Chad , Randall Troy D. , Lund Frances E. 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1158493

DOI=10.3389/fimmu.2023.1158493

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>To address whether Chi3l1 also contributes to T<sub>H</sub>2 responses following nematode infection, we infected <italic>Chi3l1</italic><sup>-/-</sup> mice with <italic>Heligmosomoides polygyrus</italic> (<italic>Hp</italic>) and analyzed T cell responses.</p></sec><sec><title>Results</title><p>As anticipated, we observed impaired T<sub>H</sub>2 responses in <italic>Hp</italic>-infected <italic>Chi3l1</italic><sup>-/-</sup> mice. However, we also found that T cell intrinsic expression of <italic>Chi3l1</italic> was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4<sup>+</sup> T<sub>FH</sub> subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for <italic>Chi3l1</italic> in T<sub>FH</sub>, germinal center B cell, and IgE responses to alum-adjuvanted vaccination. While <italic>Chi3l1</italic> was critical for IgE humoral responses it was not required for vaccine or infection-induced IgG1 responses.</p></sec><sec><title>Discussion</title><p>These results suggest that <italic>Chi3l1</italic> modulates IgE responses, which are known to be highly dependent on IL-4-producing T<sub>FH</sub> cells.</p></sec>