Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

Wanjalla, Celestine N.; McDonnell, Wyatt J.; Ramesh, Ram; Chopra, Abha; Gangula, Rama; Leary, Shay; Mashayekhi, Mona; Simmons, J. Aaron; Warren, Christian M.; Bailin, Samuel; Gabriel, Curtis L.; Guo, Liang; Furch, Briana D.; Lima, Morgan C.; Woodward, Beverly; Hannah, LaToya; Pilkinton, Mark A.; Fuller, Daniela; Kawai, Kenji; Virmani, Renu; Finn, Aloke V.; Hasty, Alyssa H.; Mallal, S.; Kalams, Spyros A.; Koethe, John R.

doi:10.1016/j.xcrm.2021.100205

Cited by 18 publications

(36 citation statements)

References 91 publications

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“…We have previously shown that in diabetic PWH, but not diabetic HIV-negative individuals, adipose tissue is enriched for CD4 + T EM and T EMRA cells co-expressing CX3CR1, GPR56, and CD57 (Wanjalla et al, 2021). We assessed CD4 + and CD8 + T cells separately to evaluate the T cell compartment.…”

Section: Resultsmentioning

confidence: 99%

“…While there was a global increase in T cells, the overall distribution of T cell subsets was relatively conserved between diabetic PWH and diabetic HIV-negative persons. We could not resolve CX3CR1 or GPR56 expression to identify CD4 + CX3CR1 + GPR56 + CD57 + cells that have previously been associated with glucose intolerance in PWH (Wanjalla et al, 2021). However, the majority of these cells are likely contained within the CD4 + T EM and T EMRA populations.…”

Section: Discussionmentioning

confidence: 97%

“…CD4 + and CD8 + T EM cells can recruit and polarize macrophages towards a CD11c + inflammatory macrophage subtype (Cho et al, 2014; Nishimura et al, 2009). One intriguing possibility is the presence of antigenic stimuli promoting CD4 + and CD8 + infiltration in PWH, potentially related to the known role of adipose tissue as a reservoir of replication-competent HIV despite plasma viral suppression, or a response to CMV reservoirs that may be inflated in PWH versus HIV- negative persons (Abana et al, 2017; Couturier et al, 2015; Wanjalla et al, 2021). Future prospective studies evaluating TCR antigen specificity, viral reservoir measurements, and functional assays are needed to assess viral-specific T cell responses in adipose tissue.…”

Section: Discussionmentioning

confidence: 99%

“…In PWH, CD4 + T cells expressing the surface markers CX3CR1, GPR56, and CD57 (C- G-C + ) that are predominately T effector memory (T EM ) and T effector memory RA (T EMRA ) phenotype accumulate in scWAT with progressive glucose intolerance. In contrast, a separate population of CD4 + T cells expressing CD69, a marker of tissue residence, (Sathaliyawala et al, 2013) predominate in scWAT of HIV-negative persons (Wanjalla et al, 2019; Wanjalla et al, 2021). Despite the importance of scWAT to metabolic health, a comprehensive assessment of the identity, polarization, and molecular programs of adipose tissue immune cells in PWH, a group at increased risk of metabolic disease, and HIV-negative individuals with glucose intolerance has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

Bailin

Kropski

Gangula

et al. 2022

Preprint

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Subcutaneous white adipose tissue (scWAT) is a critical regulator of systemic metabolic homeostasis. HIV infection is accompanied by alterations in scWAT immune cells, which may contribute to the increased risk for cardiometabolic diseases in persons with HIV (PWH) and serve as a model to investigate cellular relationships. We generated the largest molecular atlas of scWAT in humans to date from 91 individuals using paired single-cell transcriptomic and proteogenomics to determine the scWAT immune profile in non-diabetic, pre-diabetic, and diabetic PWH, and HIV-negative diabetic persons. We identified a substantial increase in lipid- associated macrophages (LAMs) with glucose intolerance, and, in PWH only, CD4+ and CD8+ T effector memory cells were correlated with LAM proportion. Finally, we resolved adipogenic and fibrogenic cells at high resolution and found a strong association between LAMs and myofibroblasts. These results provide a high-resolution, multi-platform characterization of changes in scWAT composition that occur with metabolic disease and HIV.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

Bailin

Kropski

Gangula

et al. 2022

Preprint

Self Cite

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“…Sample preparation (RNA extraction, library preparation) and sequencing was performed at the Institute for Immunology and Infectious Diseases (Murdoch University, Perth, Western Australia) using the method described in Wanjalla et al 2021 [ 27 ], which is an adapted version of the SMARTseq2 and MARS-seq approaches [ 28 , 29 ]. Briefly, the assay utilized uniquely tagged primers for reverse transcription and template switching with a pre-amplification step to increase the yield and transcript length of the single-cell cDNA library.…”

Section: Methodsmentioning

confidence: 99%

Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy

Miller

Fuller-Carter

Masarini

et al. 2022

Cell. Mol. Life Sci.

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Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite individual IRDs (Inherited retinal disease) being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6ccpfl1 mouse model of achromatopsia, a cone-specific vision loss IRD (Inherited retinal disease), to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD (Inherited retinal disease)-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in developing a broad class of novel therapies to slow cone degeneration.

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Immune Cell Activation in Obesity and Cardiovascular Disease

et al. 2022

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Purpose of Review In this review, we focus on immune cell activation in obesity and cardiovascular disease, highlighting specific immune cell microenvironments present in individuals with atherosclerosis, non-ischemic heart disease, hypertension, and infectious diseases. Recent Findings Obesity and cardiovascular disease are intimately linked and often characterized by inflammation and a cluster of metabolic complications. Compelling evidence from single-cell analysis suggests that obese adipose tissue is inflammatory and infiltrated by almost all immune cell populations. How this inflammatory tissue state contributes to more systemic conditions such as cardiovascular and infectious disease is less well understood. However, current research suggests that changes in the adipose tissue immune environment impact an individual’s ability to combat illnesses such as influenza and SARS-CoV2 . Summary Obesity is becoming increasingly prevalent globally and is often associated with type 2 diabetes and heart disease. An increased inflammatory state is a major contributor to this association. Widespread chronic inflammation in these disease states is accompanied by an increase in both innate and adaptive immune cell activation. Acutely, these immune cell changes are beneficial as they sustain homeostasis as inflammation increases. However, persistent inflammation subsequently damages tissues and organs throughout the body. Future studies aimed at understanding the unique immune cell populations in each tissue compartment impacted by obesity may hold potential for therapeutic applications.

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Single-cell analysis shows that adipose tissue of persons with both HIV and diabetes is enriched for clonal, cytotoxic, and CMV-specific CD4+ T cells

Cited by 18 publications

References 91 publications

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

White Adipose Tissue Compositional and Transcriptional Patterns with Progressive Glucose Intolerance in Persons with HIV

Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy

Immune Cell Activation in Obesity and Cardiovascular Disease

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