AUTHOR=Schuster Cornelia , Kiaf Badr , Hatzihristidis Teri , Ruckdeschel Anna , Nieves-Bonilla Janice , Ishikawa Yuki , Zhao Bin , Zheng Peilin , Love Paul E. , Kissler Stephan 

TITLE=CD5 Controls Gut Immunity by Shaping the Cytokine Profile of Intestinal T Cells

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.906499

DOI=10.3389/fimmu.2022.906499

ISSN=1664-3224

ABSTRACT=<p>CD5 is constitutively expressed on all T cells and is a negative regulator of lymphocyte function. However, the full extent of CD5 function in immunity remains unclear. CD5 deficiency impacts thymic selection and extra-thymic regulatory T cell generation, yet CD5 knockout was reported to cause no immune pathology. Here we show that CD5 is a key modulator of gut immunity. We generated mice with inducible CD5 knockdown (KD) in the autoimmune-prone nonobese diabetic (NOD) background. CD5 deficiency caused T cell-dependent wasting disease driven by chronic gut immune dysregulation. CD5 inhibition also exacerbated acute experimental colitis. Mechanistically, loss of CD5 increased phospho-Stat3 levels, leading to elevated IL-17A secretion. Our data reveal a new facet of CD5 function in shaping the T cell cytokine profile.</p>