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SHR Neuro Cancer Cardio Lipid Metab Microb

Gadjalova, I; Heinze, JM; Goess, MC; Hofmann, J; Buck, A; Weber, MC; Blissenbach, B; Kampick, M; Krut, O; Steiger, K; Janssen, KP; Neumann, PA; Ruland, J; Keppler, SJ.
B cell-mediated CD4 T-cell costimulation via CD86 exacerbates pro-inflammatory cytokine production during autoimmune intestinal inflammation.
Mucosal Immunol. 2024; 17(1):67-80 Doi: 10.1016/j.mucimm.2023.10.005
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Leading authors Med Uni Graz: Keppler Selina Jessica
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Abstract:: Dysregulated B cell responses have been described in inflammatory bowel disease (IBD) patients; however, the role of B cells in IBD pathology remained incompletely understood. We here provide evidence for the detrimental role of activated B cells during the onset of autoimmune intestinal inflammation. Using Wiskott-Aldrich Syndrome interacting protein deficient (Wipf1^-/-) mice as a mouse model of chronic colitis, we identified clusters of differentiation (CD)86 expression on activated B cells as a crucial factor exacerbating pro-inflammatory cytokine production of intestinal CD4 T cells. Depleting B cells through anti-CD20 antibody treatment or blocking costimulatory signals mediated by CD86 through cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) diminished intestinal inflammation in our mouse model of chronic IBD at the onset of disease. This was due to a reduction in aberrant humoral immune responses and reduced CD4 T cell pro-inflammatory cytokine production, especially interferon-g (IFN-g) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, in addition to B cells isolated from the inflamed colon of Wipf1^-/- mice, we also found CD86 mRNA and protein expression upregulated on activated B cells isolated from inflamed tissue of human patients with IBD. B cell activation and CD86 expression were boosted by soluble CD40L in vitro, which we found in the serum of mice and human patients with IBD. In summary, our data provides detailed insight into the contribution of B cells to intestinal inflammation, with implications for the treatment of IBD.
Find related publications in this database (using NLM MeSH Indexing): Humans - administration & dosage; CD4-Positive T-Lymphocytes - administration & dosage; Colitis - administration & dosage; Inflammation - metabolism; Inflammatory Bowel Diseases - administration & dosage; Intestinal Mucosa - administration & dosage; Intestines - pathology