Distinct immunocyte-promoting and adipocyte-generating stromal components coordinate adipose tissue immune and metabolic tenors

Regulatory T cells (T ) are key brakes on the visceral adipose tissue (VAT) inflammation that regulates local and systemic metabolic tenor. Breakdown of this regulation promotes type 2 diabetes. The cytokine IL-33 expands and sustains the unique T population residing within VAT. Here, relying on sin...

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Bibliographic Details
Published in:Science immunology 2019-05, Vol.4 (35)
Main Authors: Spallanzani, Raul German, Zemmour, David, Xiao, Tianli, Jayewickreme, Teshika, Li, Chaoran, Bryce, Paul J, Benoist, Christophe, Mathis, Diane
Format: Article
Language:English
Subjects:
Adipocytes - immunology
Animals
Diabetes Mellitus, Type 2 - immunology
Diabetes Mellitus, Type 2 - metabolism
Inflammation - immunology
Interleukin-33 - metabolism
Intra-Abdominal Fat - cytology
Intra-Abdominal Fat - immunology
Intra-Abdominal Fat - metabolism
Male
Mesenchymal Stem Cells - immunology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Obesity - immunology
Obesity - metabolism
Sequence Analysis, RNA - methods
Single-Cell Analysis - methods
T-Lymphocytes, Regulatory - immunology
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Summary:Regulatory T cells (T ) are key brakes on the visceral adipose tissue (VAT) inflammation that regulates local and systemic metabolic tenor. Breakdown of this regulation promotes type 2 diabetes. The cytokine IL-33 expands and sustains the unique T population residing within VAT. Here, relying on single-cell RNA sequencing, we identified the major IL-33 producers in VAT to be particular mesenchymal stromal cell subtypes, related to but distinct from adipocyte progenitor cells. We explored modulation of the VAT stromal cell landscape with physiologic variables such as age and sex, as well as its remodeling in pathogenic states like obesity. Last, we uncovered a VAT T :stromal cell negative regulatory loop that keeps the potent effect of IL-33 under rein.
ISSN:2470-9468
2470-9468
DOI:10.1126/sciimmunol.aaw3658