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The regulation of erythroid progenitors and T cells by CD45

University of British Columbia

The immune system plays a crucial role in the protection of the host against infection and the maintenance of homeostasis under normal conditions. This is achieved by cooperative work amongst a diverse population of immune cells. The pan-leukocyte marker CD45 is a receptor-type tyrosine phosphatase expressed on all nucleated hematopoietic cells. While the function of CD45 on adaptive immune cells has been well described, the role of CD45 on innate immune cells and erythroid progenitors is less understood. CD71⁺TER119⁺ erythroid progenitors are prevalent in neonates; in addition to generating mature erythrocytes, they create an immunosuppressive environment. Here, I show that CD45 regulates late erythroid development as CD45-deficient mice maintained a high level of CD71⁺TER119⁺ progenitor cells in the spleen into adulthood. Despite the increase, CD45-deficient mice had normal numbers of mature red blood cells (RBCs) due to increased sensitivity of erythroid progenitors to erythropoietin (EPO) and an increased number of EPO-producing red pulp macrophages (RPMs). Increased CD71⁺TER119⁺ cells in CD45-deficient RAGKO mice (CD45RAGKO) had an impact on the outcome of T cell transfer colitis. CD45RAGKO had delayed systemic wasting and reduced TNFα production by splenic myeloid cells despite having an equal level of inflammation in the colon. Adoptive transfer of erythroid progenitors from CD45RAGKO donor into RAGKO attenuated the weight loss and reduced TNFα expression by RPMs. Co-culturing of erythroid cells suppressed TNFα expression from RPMs in a phagocytosis-dependent manner. These findings implicate CD45 as a positive regulator of systemic inflammation and suggest erythroid progenitors are an anti-inflammatory agent in colitis.

Text

2021-04-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/74321

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/