The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Visceral Adipose Inflammation in Obesity Is Associated with Critical Alterations in Tregulatory Cell Numbers
Open accessAbstract
BACKGROUND: The development of insulin resistance (IR) in mouse models of obesity and type 2 diabetes mellitus (DM) is characterized by progressive accumulation of inflammatory macrophages and subpopulations of T cells in the visceral adipose. Regulatory T cells (Tregs) may play a critical role in modulating tissue inflammation via their interactions with both adaptive and innate immune mechanisms. We hypothesized that an imbalance in Tregs is a critical determinant of adipose inflammation and investigated the role of Tregs in IR/obesity through coordinated studies in mice and humans. METHODS AND FINDINGS: Foxp3-green fluorescent protein (GFP) "knock-in" mice were randomized to a high-fat diet intervention for a duration of 12 weeks to induce DIO/IR. Morbidly obese humans without overt type 2 DM (n = 13) and lean controls (n = 7) were recruited prospectively for assessment of visceral adipose inflammation. DIO resulted in increased CD3(+)CD4(+), and CD3(+)CD8(+) cells in visceral adipose with a striking decrease in visceral adipose Tregs. Treg numbers in visceral adipose inversely correlated with CD11b(+)CD11c(+) adipose tissue macrophages (ATMs). Splenic Treg numbers were increased with up-regulation of homing receptors CXCR3 and CCR7 and marker of activation CD44. In-vitro differentiation assays showed an inhibition of Treg differentiation in response to conditioned media from inflammatory macrophages. Human visceral adipose in morbid obesity was characterized by an increase in CD11c(+) ATMs and a decrease in foxp3 expression. CONCLUSIONS: Our experiments indicate that obesity in mice and humans results in adipose Treg depletion. These changes appear to occur via reduced local differentiation rather than impaired homing. Our findings implicate a role for Tregs as determinants of adipose inflammation.
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Cites
Two subsets of memory T lymphocytes with distinct homing potentials and effector functions
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“Therefore, we analyzed surface expression of chemokine homing receptors CXCR3 and CCR7 on T cells in spleen and mesenteric lymph nodes (Figure 4A, B, D), two receptors previously described to regulate the trafficking of Tregs [17,18,19].”
MethodRegulatory T Cells and Immune Tolerance
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Self-citationCD44: From adhesion molecules to signalling regulators
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Normalization of obesity-associated insulin resistance through immunotherapy
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Cited by
Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes
Esser, N., Legrand-Poels, S., Piette, J., Scheen, A. J., & Paquot, N. (2014) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2014.04.006 · Cited by 1,981
Adipose tissue inflammation and metabolic dysfunction in obesity
Kawai, T., Autieri, M. V., & Scalia, R. (2021) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00379.2020 · Cited by 1,947
Makki, K., Froguel, P., & Wolowczuk, I. (2013) · ISRN Inflammation · doi:10.1155/2013/139239 · Cited by 1,085
Wang, Z., Aguilar, E. G., Luna, J. I., Dunai, C., Khuat, L. T., Le, C. T., Mirsoian, A., Minnar, C. M., Stoffel, K. M., Sturgill, I. R., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0221-5 · Cited by 865
Adipokine dysregulation and adipose tissue inflammation in human obesity
Unamuno, X., Gómez‐Ambrosi, J., Rodríguez, A., Becerril, S., Frühbeck, G., & Catalán, V. (2018) · European Journal of Clinical Investigation · doi:10.1111/eci.12997 · Cited by 610
Metadata
- Authors
- Deiuliis, J., Shah, Z., Shah, N., Needleman, B., Mikami, D., Narula, V., Perry, K., Hazey, J., Kampfrath, T., Kollengode, M., Sun, Q., Satoskar, A. R., Lumeng, C., Moffatt-Bruce, S., & Rajagopalan, S.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-01-26
- Volume
- 6
- Issue
- 1
- Pages
- e16376
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2008381613
- Cited by
- 314
- References
- 44
- FWCI
- 19.02
- Type
- journal article
- Language
- en
- Open access
- gold
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- Deiuliis, J., Shah, Z., Shah, N., Needleman, B., Mikami, D., Narula, V., Perry, K., Hazey, J., Kampfrath, T., Kollengode, M., Sun, Q., Satoskar, A. R., Lumeng, C., Moffatt-Bruce, S., & Rajagopalan, S. (2011). Visceral Adipose Inflammation in Obesity Is Associated with Critical Alterations in Tregulatory Cell Numbers. PLoS ONE. https://doi.org/10.1371/journal.pone.0016376
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