TY  - JOUR
AU  - Huard, Arnaud
AU  - Wilmes, Christian
AU  - Kiprina, Anastasiia
AU  - Netzer, Christoph
AU  - Palmer, Gaby
AU  - Brüne, Bernhard
AU  - Weigert, Andreas
TI  - Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production.
JO  - International journal of molecular sciences
VL  - 24
IS  - 6
SN  - 1422-0067
CY  - Basel
PB  - Molecular Diversity Preservation International
M1  - DKFZ-2023-00637
SP  - 5676
PY  - 2023
AB  - IL-38 is an IL-1 family receptor antagonist with an emerging role in chronic inflammatory diseases. IL-38 expression has been mainly observed not only in epithelia, but also in cells of the immune system, including macrophages and B cells. Given the association of both IL-38 and B cells with chronic inflammation, we explored if IL-38 affects B cell biology. IL-38-deficient mice showed higher amounts of plasma cells (PC) in lymphoid organs but, conversely, lower levels of plasmatic antibody titers. Exploring underlying mechanisms in human B cells revealed that exogenously added IL-38 did not significantly affect early B cell activation or differentiation into plasma cells, even though IL-38 suppressed upregulation of CD38. Instead, IL-38 mRNA expression was transiently upregulated during the differentiation of human B cells to plasma cells in vitro, and knocking down IL-38 during early B cell differentiation increased plasma cell generation, while reducing antibody production, thus reproducing the murine phenotype. Although this endogenous role of IL-38 in B cell differentiation and antibody production did not align with an immunosuppressive function, autoantibody production induced in mice by repeated IL-18 injections was enhanced in an IL-38-deficient background. Taken together, our data suggest that cell-intrinsic IL-38 promotes antibody production at baseline but suppresses the production of autoantibodies in an inflammatory context, which may partially explain its protective role during chronic inflammation.
KW  - B cell differentiation (Other)
KW  - IL-1 family (Other)
KW  - IL-38 (Other)
KW  - antibodies (Other)
KW  - autoimmunity (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36982750
DO  - DOI:10.3390/ijms24065676
UR  - https://inrepo02.dkfz.de/record/274560
ER  -