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Publication : Splenic erythroid progenitors decrease TNF-α production by macrophages and reduce systemic inflammation in a mouse model of T cell-induced colitis.

First Author  Shim YA Year  2021
Journal  Eur J Immunol Volume  51
Issue  3 Pages  567-579
PubMed ID  33180325 Mgi Jnum  J:304441
Mgi Id  MGI:6508635 Doi  10.1002/eji.202048687
Citation  Shim YA, et al. (2021) Splenic erythroid progenitors decrease TNF-alpha production by macrophages and reduce systemic inflammation in a mouse model of T cell-induced colitis. Eur J Immunol 51(3):567-579
abstractText  In inflammatory bowel disease (IBD), inflammation can occur beyond the intestine and spread systemically causing complications such as arthritis, cachexia, and anemia. Here, we determine the impact of CD45, a pan-leukocyte marker and tyrosine phosphatase, on IBD. Using a mouse model of T cell transfer colitis, CD25(-) CD45RB(high) CD4(+) T cells were transferred into Rag1-deficient mice (RAGKO) and CD45-deficient RAGKO mice (CD45RAGKO). Weight loss and systemic wasting syndrome were delayed in CD45RAGKO mice compared to RAGKO mice, despite equivalent inflammation in the colon. CD45RAGKO mice had reduced serum levels of TNF-alpha, and reduced TNF-alpha production by splenic myeloid cells. CD45RAGKO mice also had increased numbers of erythroid progenitors in the spleen, which had previously been shown to be immunosuppressive. Adoptive transfer of these erythroid progenitors into RAGKO mice reduced their weight loss and TNF-alpha expression by splenic red pulp macrophages. In vitro, erythroid cells suppressed TNF-alpha expression in red pulp macrophages in a phagocytosis-dependent manner. These findings show a novel role for erythroid progenitors in suppressing the pro-inflammatory function of splenic macrophages and cachexia associated with IBD.
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