CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity
Abstract
Inflammation is increasingly regarded as a key process underlying metabolic diseases in obese individuals. In particular, obese adipose tissue shows features characteristic of active local inflammation. At present, however, little is known about the sequence of events that comprises the inflammatory cascade or the mechanism by which inflammation develops. We found that large numbers of CD8(+) effector T cells infiltrated obese epididymal adipose tissue in mice fed a high-fat diet, whereas the numbers of CD4(+) helper and regulatory T cells were diminished. The infiltration by CD8(+) T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8(+) T cells lowered macrophage infiltration and adipose tissue inflammation and ameliorated systemic insulin resistance. Conversely, adoptive transfer of CD8(+) T cells to CD8-deficient mice aggravated adipose inflammation. Coculture and other in vitro experiments revealed a vicious cycle of interactions between CD8(+) T cells, macrophages and adipose tissue. Our findings suggest that obese adipose tissue activates CD8(+) T cells, which, in turn, promote the recruitment and activation of macrophages in this tissue. These results support the notion that CD8(+) T cells have an essential role in the initiation and propagation of adipose inflammation.
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Previous studies revealed that CTLs could promote the recruitment and activation of macrophages during inflammation.
“Previous studies revealed that CTLs could promote the recruitment and activation of macrophages during inflammation.48”
CD8+ T cell infiltration can precede and induce adipose tissue macrophage accumulation in some settings.
“as CD8 + T cell infiltration has been observed to precede and induce AT macrophage accumulation in other settings (11).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [11]
Levels of a specific subpopulation of CD8+ T cells are enriched in the early stages of obesity, preceding the accumulation of adipose tissue macrophages.
“In particular, levels of a specific subpopulation of CD8 + T cells are enriched in the early stages of obesity, in fact preceding the accumulation of ATMΦs (56).”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [56]
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“Humans easily eat more calories than they can expend (O’Rahilly, 2016).”
Background
- Authors
- Nishimura, S., Manabe, I., Nagasaki, M., Eto, K., Yamashita, H., Ohsugi, M., Otsu, M., Hara, K., Ueki, K., Sugiura, S., Yoshimura, K., Kadowaki, T., & Nagai, R.
- Affiliations
- The University of Tokyo (JP)
- Japan Science and Technology Agency (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Nishimura, Satoshi
- Manabe, Ichiro
- ORCID
- Venue
- Nature Medicine
- Published
- 2009-07-26
- Volume
- 15
- Issue
- 8
- Pages
- 914-920
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2165334726
- Cited by
- 2,230
- References
- 24
- Citations by year
- 2026: 64 · 2025: 83 · 2024: 108 · 2023: 106 · 2022: 123 · 2021: 170 · 2020: 133 · 2019: 130 · 2018: 138 · 2017: 158 · 2016: 147 · 2015: 148 · 2014: 140 · 2013: 198 · 2012: 131
- FWCI
- 86.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (21390278, 21390321)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Keywords
- CD8+ effector T cells, macrophage recruitment, adipose tissue inflammation, obesity, insulin resistance, macrophage-T cell interaction, high-fat diet, CD4+ T helper cells, regulatory T cells, obesity-related diabetes
- MeSH terms
- Adipose Tissue, Animals, Cell Movement, Chemotaxis, Leukocyte, Diet, Atherogenic, Inflammation, Macrophages, Mice, Inbred C57BL, Mice, Obese, Obesity, Down-Regulation, Adipocytes, CD8-Positive T-Lymphocytes, Lymphocyte Count, Mice
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