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CC BY V4.0, Open Access
Journal article
Changes in subcutaneous white adipose tissue cellular composition and molecular programs underlie glucose intolerance in persons with HIV
Frontiers in immunology, Vol.14
2023
Abstract
Introduction: Subcutaneous adipose tissue (SAT) is a critical regulator of systemic metabolic homeostasis. Persons with HIV (PWH) have an increased risk of metabolic diseases and significant alterations in the SAT immune environment compared with the general population.
Methods: We generated a comprehensive single-cell multi-omic SAT atlas to characterize cellular compositional and transcriptional changes in 59 PWH across a spectrum of metabolic health.
Results: Glucose intolerance was associated with increased lipid-associated macrophages, CD4+ and CD8+ T effector memory cells, and decreased perivascular macrophages. We observed a coordinated intercellular regulatory program which enriched for genes related to inflammation and lipid-processing across multiple cell types as glucose intolerance increased. Increased CD4+ effector memory tissue-resident cells most strongly associated with altered expression of adipocyte genes critical for lipid metabolism and cellular regulation. Intercellular communication analysis demonstrated enhanced pro-inflammatory and pro-fibrotic signaling between immune cells and stromal cells in PWH with glucose intolerance compared with non-diabetic PWH. Lastly, while cell type-specific gene expression among PWH with diabetes was globally similar to HIV-negative individuals with diabetes, we observed substantially divergent intercellular communication pathways.
Discussion: These findings suggest a central role of tissue-resident immune cells in regulating SAT inflammation among PWH with metabolic disease, and underscore unique mechanisms that may converge to promote metabolic disease.
Details
- Title
- Changes in subcutaneous white adipose tissue cellular composition and molecular programs underlie glucose intolerance in persons with HIV
- Authors/Creators
- Samuel S. Bailin - Vanderbilt University Medical CenterJonathan A. Kropski - Vanderbilt University Medical CenterRama D. Gangula - Vanderbilt University Medical CenterLaToya Hannah - Vanderbilt University Medical CenterJoshua D. Simmons - , , , , , , , , , , , , , , , , , , , , , , , ,Mona Mashayekhi - Vanderbilt University Medical CenterFei Ye - Vanderbilt University Medical CenterRun Fan - , , , , , , , , , , , , , , , , , , , , , , , ,Simon Mallal - , , , , , , , , , , , , , , , , , , , , , , , ,Christian M. Warren - Vanderbilt University Medical CenterSpyros A. Kalams - Vanderbilt University Medical CenterCurtis L. Gabriel - Vanderbilt University Medical CenterCelestine N. Wanjalla - Vanderbilt University Medical CenterJohn R. Koethe - Vanderbilt University Medical Center
- Publication Details
- Frontiers in immunology, Vol.14
- Publisher
- Frontiers Media S.A
- Identifiers
- 991005605568707891
- Copyright
- © 2023 Bailin et al.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.66 HIV
- 1.66.1372 HIV Comorbidities
- Web Of Science research areas
- Immunology
- ESI research areas
- Immunology