Postdoctoral Fellow Vanderbilt Univ. Med. Ctr., United States
Disclosure(s):
Ronald McMillan, PhD: No financial relationships to disclose
Introduction/Rationale: People living with HIV (PLWH) are at a greater risk of developing cardiometabolic diseases, including diabetes, compared with people without HIV (PWoH). Chemerin (RARRES2), regulates immunity and metabolism through its receptors CMKLR1 and CCRL2. We hypothesized that chemerin–CMKLR1 signaling is dysregulated in PLWH, contributing to metabolic disease.
Methods: We analyzed chemerin in the adipose tissue from 59 PWH (20 non-diabetic, 19 prediabetic, and 20 diabetic) in the HATIM cohort. Single-cell transcriptomic analysis was used to compare CMKLR1 expression based on HIV status and to identify differential gene expression in smooth muscle cells.
Results: CMKLR1 was highly expressed in stromal/myeloid cells, while RARRES2 was expressed in preadipocytes and vascular smooth muscle cells. Macrophage CMKLR1 expression was increased in PLWH with diabetes (P=0.0002) compared to PWoH with diabetes, while CCRL2 trended higher (P=0.09). Communication analysis showed HIV shifts signaling from structural/homeostatic pathways (COLLAGEN, CD99, ANNEXIN) toward inflammatory/metabolic axes (CHEMERIN, GAS6, ICAM). In the CHEMERIN pathway, preadipocytes predicted as the dominant senders. Intermediate macrophages and myofibroblasts were the principal receivers.
Conclusion: Chemerin–CMKLR1 signaling is upregulated in PLWH, particularly within inflammatory macrophages, suggesting enhanced immune–stromal crosstalk that may underlie the heightened risk of diabetes and cardiometabolic disease in this population.
