High fat diet modulates conventional dendritic cell development through Interferon regulatory factor 8

Abstract

During obesity-associated inflammation, myeloid cells play an essential role in initiating and maintaining inflammation during diet-induced obesity. In recent years, more evidence has linked conventional dendritic cell (cDC) to the state of inflammation in obesity. Identification of cDC subsets in the context of obesity has been challenging due to ambiguous marker expression. This study's objective was to understand how XCR1⁺ cDC1 develops under diet-induced obesity (DIO). To understand the development of cDC1, I analyzed the progenitors of cDCs in the bone marrow and blood to understand the potential mechanisms of how DIO influence DC progenitors. I analyzed the transcription factors controlling DC progenitors to understand how DIO can impact their cell fate. I developed a new gating strategy to define cDC subsets in the ADT based on XCR1⁺ (cDC1) and CD172a⁺ (cDC2) to compare our findings with previous studies that, in contrast, defined cDCs in the ADT as CD103⁺ (cDC1) and CD11b⁺ (cDC2). This work reveals how DIO modulates cDC1 development and maturation, showing that cDC development is sensitive to nutritional changes. Also, the results present in my thesis work imply that disease complications during obesity like lung infection and tumor may be due to defect in cDC1 development. Finally, cDC1 can play a role in the control of inflammation in adipose tissue during obesity.