Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 51, Issue 3, Pages 567-579Publisher
WILEY
DOI: 10.1002/eji.202048687
Keywords
CD45; colitis; erythroid progenitors; IBD; wasting disease
Categories
Funding
- Canadian Institutes of Health Research [MOP-77712]
- Natural Sciences and Engineering Research Council
- 4-year UBC graduate student fellowship
- Canadian Institutes of Health Research Banting and Best Master's studentship
- Canadian Digestive Health Foundation
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The study shows an important role of CD45 in IBD, where CD45-deficient mice experienced less weight loss and systemic wasting syndrome when subjected to T cell transfer colitis, along with reduced levels of serum TNF-alpha. The findings suggest a novel role for erythroid progenitors in suppressing pro-inflammatory function of splenic macrophages and cachexia associated with IBD.
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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