Date on Master's Thesis/Doctoral Dissertation

8-2020

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Microbiology and Immunology

Degree Program

Microbiology and Immunology, PhD

Committee Chair

Hoying, James B.

Committee Co-Chair (if applicable)

Alard, Pascale

Committee Member

Mitchell, Thomas

Committee Member

Yan, Jun

Committee Member

LeBlanc, Amanda

Abstract

Our goal with this study was to gain insight into the homeostatic immune cell network in healthy adipose tissue. Specifically, we sought to determine if the immature myeloid cells found in healthy and inflamed adipose were, in fact, tissue-resident myeloid-derived suppressor cells (MDSCs). Using various in vitro and in vivo methods, we have uncovered a population of CD11bHi Ly6CHi Ly6G- MDSCs resident in healthy adipose tissue. To the best of our knowledge this is the first time that these cells have been investigated and described in healthy adipose tissue. Systemic MDSC depletion lead to the accumulation of CD4+ CD44+ CD62L- TEM in the adipose of otherwise healthy mice and altered the surface markers expressed by adipose tissue-resident macrophages. Furthermore, we found that losing MDSCs significantly changed the transcription levels of multiple immunomodulatory genes in the adipose stromal cell compartment and whole adipose tissue. Taken together, this suggests that adipose-resident MDSCs are one of the key players in the adipose tissue immune cell network, preventing aberrant, inflammatory TEM proliferation and modulating the suppressive phenotype of adipose tissue-resident macrophages.

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