Author ORCID Identifier

https://orcid.org/0000-0003-1518-8774

Date of Award

12-10-2018

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

First Advisor

Yuan Liu MD,PhD

Second Advisor

Bingzhong Xue PhD

Third Advisor

Timothy Denning PhD

Abstract

According to Bian et al., polymorphonuclear leukocytes (PMN) undergo phenotypic changes, suggestive of bone marrow (BM) myeloid reprogramming, under chronic inflammatory conditions 1. Utilizing a murine dextran sodium sulfate (DSS)-induced colitis-to-recovery model, we characterized the BM myeloid compartment during acute, post-acute/chronic, and resolution of inflammation. Percoll density gradient separation of BM leukocytes from colitis-to-recovery mice revealed significant expansion of the immature myeloid compartment (IMC) beginning at the post-acute stage and extending until after complete inflammation resolution. Additionally, we show that both the mature PMN and immature myeloid populations increased production of reactive oxygen species (ROS) and demonstrated enhanced infiltration during zymosan-induced peritonitis. Interestingly, the expanded immature granulocytes not only expressed CXCR2 and ARG-1, but also demonstrated potent inhibition of T cell proliferation. These findings suggest that the myeloid compartment undergoes reprogramming at the post-acute phase producing functionally primed PMN that accelerate pathogen clearance, as well as immature Ly6G+CXCR2high immunosuppressive effector cells that likely play a role in inflammation recovery and tissue repair. Our study could provide novel strategies for treatment of chronic inflammatory diseases such as ulcerative colitis.

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