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Publication
Granzyme B prevents aberrant IL-17 production and intestinal pathogenicity in
CD4+ T cells.
Authors Hoek KL, Greer MJ, McClanahan KG, Nazmi A, Piazuelo MB, Singh K, Wilson KT,
Olivares-Villagómez D
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Mucosal immunology
Year 2021
Date Published 9/1/2021
Volume : Pages 14 : 1088 - 1099
PubMed Reference 34183776
Abstract CD4+ T cell activation and differentiation are important events that set the
stage for proper immune responses. Many factors are involved in the activation
and differentiation of T cells, and these events are tightly controlled to
prevent unwanted and/or exacerbated immune responses that may harm the host. It
has been well-documented that granzyme B, a potent serine protease involved in
cell-mediated cytotoxicity, is readily expressed by certain CD4+ T cells, such
as regulatory T cells and CD4+CD8aa+ intestinal intraepithelial lymphocytes,
both of which display cytotoxicity associated with granzyme B. However, because
not all CD4+ T cells expressing granzyme B are cytotoxic, additional roles for
this protease in CD4+ T cell biology remain unknown. Here, using a combination
of in vivo and in vitro approaches, we report that granzyme B-deficient CD4+ T
cells display increased IL-17 production. In the adoptive transfer model of
intestinal inflammation, granzyme B-deficient CD4+ T cells triggered a more
rapid disease onset than their WT counterparts, and presented a differential
transcription profile. Similar results were also observed in granzyme
B-deficient mice infected with Citrobacter rodentium. Our results suggest that
granzyme B modulates CD4+ T cell differentiation, providing a new perspective
into the biology of this enzyme.




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