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

• Authors: Miranda L. Curtiss, University of Alabama Birmingham; Alexander F. Rosenberg, University of Alabama Birmingham; Christopher Scharer, Emory University; Betty Mousseau, University of Alabama Birmingham; Natalia A. Ballesteros Benavides, University of Alabama Birmingham; John E. Bradley, University of Alabama Birmingham; Beatriz Leon, University of Alabama Birmingham; Chad Steele, Tulane University; Troy D. Randall, University of Alabama Birmingham; Frances E. Lund, University of Alabama Birmingham
• Journal Title: FRONTIERS IN IMMUNOLOGY
• Volume: Volume 14
• Publisher: FRONTIERS MEDIA SA | 2023-07-27, Pages 1158493-1158493
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.3389/fimmu.2023.1158493
• Subjects: Health Sciences, Immunology; Biology, Genetics; Biology, Cell
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; IgE (immunoglobulin E); helminth; germinal center; T follicular helper (T cell FH; T helper 2 (Th2) cells; enteric; IL-4; germinal center (GC) B cells; FOLLICULAR HELPER-CELL; SERUM YKL-40; PROTECTIVE IMMUNITY; GENETIC-VARIATION; ICOS EXPRESSION; CHITIN; DIFFERENTIATION; INFLAMMATION; PROTEINS; CHI3L1

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 TH2 responses following nematode infection, we infected Chi3l1-/- mice with Heligmosomoides polygyrus (Hp) and analyzed T cell responses. Results: As anticipated, we observed impaired TH2 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+ TFH subset, which supports germinal center B cell reactions and IgE responses. We also observed roles for Chi3l1 in TFH, 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 TFH cells.