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@ARTICLE{Huard:274560,
author = {A. Huard and C. Wilmes and A. Kiprina and C. Netzer and G.
Palmer and B. Brüne$^*$ and A. Weigert$^*$},
title = {{C}ell {I}ntrinsic {IL}-38 {A}ffects {B} {C}ell
{D}ifferentiation and {A}ntibody {P}roduction.},
journal = {International journal of molecular sciences},
volume = {24},
number = {6},
issn = {1422-0067},
address = {Basel},
publisher = {Molecular Diversity Preservation International},
reportid = {DKFZ-2023-00637},
pages = {5676},
year = {2023},
abstract = {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.},
keywords = {B cell differentiation (Other) / IL-1 family (Other) /
IL-38 (Other) / antibodies (Other) / autoimmunity (Other)},
cin = {FM01},
ddc = {540},
cid = {I:(DE-He78)FM01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36982750},
doi = {10.3390/ijms24065676},
url = {https://inrepo02.dkfz.de/record/274560},
}