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Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production

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...

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Autores principales: Huard, Arnaud, Wilmes, Christian, Kiprina, Anastasiia, Netzer, Christoph, Palmer, Gaby, Brüne, Bernhard, Weigert, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053218/
https://www.ncbi.nlm.nih.gov/pubmed/36982750
http://dx.doi.org/10.3390/ijms24065676
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author Huard, Arnaud
Wilmes, Christian
Kiprina, Anastasiia
Netzer, Christoph
Palmer, Gaby
Brüne, Bernhard
Weigert, Andreas
author_facet Huard, Arnaud
Wilmes, Christian
Kiprina, Anastasiia
Netzer, Christoph
Palmer, Gaby
Brüne, Bernhard
Weigert, Andreas
author_sort Huard, Arnaud
collection PubMed
description 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.
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spelling pubmed-100532182023-03-30 Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production Huard, Arnaud Wilmes, Christian Kiprina, Anastasiia Netzer, Christoph Palmer, Gaby Brüne, Bernhard Weigert, Andreas Int J Mol Sci Article 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. MDPI 2023-03-16 /pmc/articles/PMC10053218/ /pubmed/36982750 http://dx.doi.org/10.3390/ijms24065676 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huard, Arnaud
Wilmes, Christian
Kiprina, Anastasiia
Netzer, Christoph
Palmer, Gaby
Brüne, Bernhard
Weigert, Andreas
Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
title Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
title_full Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
title_fullStr Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
title_full_unstemmed Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
title_short Cell Intrinsic IL-38 Affects B Cell Differentiation and Antibody Production
title_sort cell intrinsic il-38 affects b cell differentiation and antibody production
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10053218/
https://www.ncbi.nlm.nih.gov/pubmed/36982750
http://dx.doi.org/10.3390/ijms24065676
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