AN AGE-DEPENDENT EXPANSION OF GAMMA DELTA T CELLS IN VISCERAL ADIPOSE TISSUE PROMOTES INFLAMMATION

The immune competent abdominal adipose tissue, either stored viscerally [visceral adipose tissue (VAT)] or sc [sc adipose tissue (SAT)], has been identified as a source of IL-1β and IL-18. To become active, the proforms of these cytokines require processing by caspase-1, which itself is mediated by the inflammasome. In this descriptive study, we investigate the expression of inflammasome components and caspase-1 in human fat and determine whether caspase-1 activity contributes to the enhanced inflammatory status of VAT. Paired SAT and VAT biopsies from 10 overweight subjects (body mass index, 25–28 kg/m2) were used to study the cellular composition and the intrinsic inflammatory capacity of both adipose tissue depots. The percentage of CD8+ T cells within the lymphocyte fraction was significantly higher in VAT compared with SAT (41.6 vs. 30.4%; P < 0.05). Adipose tissue cultures showed a higher release of IL-1β (10-fold; P < 0.05), IL-18 (3-fold; P < 0.05), and IL-6 and IL-8 (3-fold, P < 0.05; and 4-fold, P < 0.05, respectively) from VAT compared with SAT that was significantly reduced by inhibiting caspase-1 activity. In addition, caspase-1 activity was 3-fold (P < 0.05) higher in VAT compared with SAT, together with an increase in the protein levels of the inflammasome members apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain (2-fold; P < 0.05) and nucleotide-binding oligomerization domain- like receptor pyrin domain containing 3 (2-fold; nonsignificant). Finally, caspase-1 activity levels were positively correlated with the percentage of CD8+ T cells present in adipose tissue. Our results show that caspase-1 and nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 inflammasome members are abundantly present in human VAT. The increased intrinsic caspase-1 activity in VAT represents a novel and specific inflammatory pathway that may determine the proinflammatory character of this specific depot.

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Faculty Opinions recommendation of Aging is associated with an increase in T cells and inflammatory macrophages in visceral adipose tissue.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717949620.793454826 ◽

2012 ◽

Author(s):

Dennis Taub ◽

Ana Lustig

Keyword(s):

T Cells ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Inflammatory Macrophages ◽

Visceral Adipose

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The effect of caloric restriction on the increase in senescence-associated T cells and metabolic disorders in aged mice

PLoS ONE ◽

10.1371/journal.pone.0252547 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252547

Author(s):

Xiaoxiang Yan ◽

Natsumi Imano ◽

Kayoko Tamaki ◽

Motoaki Sano ◽

Ken Shinmura

Keyword(s):

Insulin Resistance ◽

T Cells ◽

Adipose Tissue ◽

T Cell ◽

Caloric Restriction ◽

Visceral Adipose Tissue ◽

Aged Mice ◽

Age Related ◽

Visceral Adipose

Aging is associated with functional decline in the immune system and increases the risk of chronic diseases owing to smoldering inflammation. In the present study, we demonstrated an age-related increase in the accumulation of Programmed Death-1 (PD-1)+ memory-phenotype T cells that are considered “senescence-associated T cells” in both the visceral adipose tissue and spleen. As caloric restriction is an established intervention scientifically proven to exert anti-aging effects and greatly affects physiological and pathophysiological alterations with advanced age, we evaluated the effect of caloric restriction on the increase in this T-cell subpopulation and glucose tolerance in aged mice. Long-term caloric restriction significantly decreased the number of PD-1+ memory-phenotype cluster of differentiation (CD) 4+ and CD8+ T cells in the spleen and visceral adipose tissue, decreased M1-type macrophage accumulation in visceral adipose tissue, and improved insulin resistance in aged mice. Furthermore, the immunological depletion of PD-1+ T cells reduced adipose inflammation and improved insulin resistance in aged mice. Taken together with our previous report, these results indicate that senescence-related T-cell subpopulations are involved in the development of chronic inflammation and insulin resistance in the context of chronological aging and obesity. Thus, long-term caloric restriction and specific deletion of senescence-related T cells are promising interventions to regulate age-related chronic diseases.

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Abstract 791: T cells in visceral adipose tissue: A potential source of inflammation to drive tumorigenesis

10.1158/1538-7445.am2011-791 ◽

2011 ◽

Author(s):

Joanne Lysaght ◽

Emma H. Allott ◽

Claire L. Donohoe ◽

Julia M. Howard ◽

Graham P. Pidgeon ◽

...

Keyword(s):

T Cells ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Potential Source ◽

Visceral Adipose

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Low visceral adipose tissue regulatory T cells are associated with higher comorbidity severity in patients undergoing bariatric surgery

Surgical Endoscopy ◽

10.1007/s00464-020-07751-w ◽

2020 ◽

Author(s):

Anahita Jalilvand ◽

Alecia Blaszczak ◽

David Bradley ◽

Joey Liu ◽

Valerie Wright ◽

...

Keyword(s):

Bariatric Surgery ◽

T Cells ◽

Adipose Tissue ◽

Regulatory T Cells ◽

Visceral Adipose Tissue ◽

Visceral Adipose

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UNIQUE TRANSCRIPTOME OF AGE-ASSOCIATED VISCERAL FAT-RESIDENT GAMMA DELTA T CELLS

Innovation in Aging ◽

10.1093/geroni/igz038.3496 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S964-S964

Author(s):

Marlene E Starr

Keyword(s):

Gene Expression ◽

T Cells ◽

Visceral Fat ◽

Cell Function ◽

Gamma Delta T Cells ◽

Gamma Delta ◽

Age Related ◽

Age Dependent ◽

High Representation

Abstract Gamma delta T cells (Tγδ) are a unique group of immune cells that perform both adaptive and innate functions. We recently identified a population of Tγδ cells which show an age-dependent expansion in the visceral fat of both mice and humans. However, little is known regarding the role of these cells in the fat. The purpose of this study was to begin delineating their role by: (1) comparing the gene expression profile of visceral fat-resident Tγδ to conventional T cells (Tconv) and to circulating Tγδ, and (2) identifying age-dependent changes in gene expression within the visceral fat-resident Tγδ population. Tγδ and Tconv were magnetically purified from blood and visceral fat of young and aged mice. Using NanoString technology, we found that overall transcriptomes of Tγδ in fat and blood were strikingly different. Transcriptomes of Tγδ and Tconv within the fat were more similar, but distinct with the former having high representation of pathways related to inflammation, cytokine and chemokine signaling, and macrophage function and the latter having high representation of pathways related to T- and B-cell function and TNF superfamily. Within the Tγδ population we identified significant (>1.8-fold change, p<0.01) age-associated differences in expression for 8 upregulated genes (C6, Cxcl13, Prg2, Il5ra, Ctla4, Marco, Ccl8, Il10) and 10 downregulated genes (Col4a1, Xcl1, Col1a1, Cfd, Col3a1, Lbp, Thbs1, Klrd1, Il6st, Ccl17). These genes will guide further research aimed at understanding the role of these cells and how their age-associated changes contribute to chronic inflammation, an underlying component of multiple age-related diseases.

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