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Cutting Edge: IL-25 Elicits Innate Lymphoid Type 2 and Type II NKT Cells That Regulate Obesity in Mice
Open accessAbstract
The cellular composition of visceral adipose tissue (VAT) and release of cytokines by such cells within VAT has been implicated in regulating obesity and metabolic homeostasis. We show the importance of IL-25–responsive innate cells, which release the Th2 cytokine IL-13, in regulating weight and glucose homeostasis in mouse models of diet-induced obesity. Treating obese mice with IL-25 induces weight loss and improves glucose tolerance, and is associated with increased infiltration of innate lymphoid type 2 cells (ILC2), type I and type II NKT cells, eosinophils, and alternatively activated macrophages into the VAT. By depleting ILC2 in obese Rag1−/− mice, we observe exacerbated weight gain and glucose intolerance. Conversely, transferring ILC2 or type I or type II NKT cells into obese mice induces transient weight loss and stabilizes glucose homeostasis. Our data identify a mechanism whereby IL-25 eliciting IL-13–producing innate cells regulates inflammation in adipose tissue and prevents diet-induced obesity.
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Cites
Obesity induces a phenotypic switch in adipose tissue macrophage polarization
Lumeng, C. N., Bodzin, J. L., & Saltiel, A. R. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29881 · Cited by 4,664
Finucane, M. M., Stevens, G. A., Cowan, M. J., Danaei, G., Lin, J. K., Paciorek, C. J., Singh, G. M., Gutierrez, H. R., Lu, Y., Bahalim, A. N., et al. (2011) · The Lancet · doi:10.1016/s0140-6736(10)62037-5 · Cited by 4,050
Macrophage-mediated inflammation in metabolic disease
Chawla, A., Nguyen, K. D., & Goh, Y. P. S. (2011) · Nature reviews. Immunology · doi:10.1038/nri3071 · Cited by 1,314
Innate lymphoid cells promote lung-tissue homeostasis after infection with influenza virus
Monticelli (2011) · PubMed · doi:10.1031/ni.2131 · Cited by 1,286
Mjösberg, J. M., Trifari, S., Crellin, N. K., Peters, C. P., van Drunen, C. M., Piet, B., Fokkens, W. J., Cupedo, T., & Spits, H. (2011) · Nature Immunology · doi:10.1038/ni.2104 · Cited by 1,166
Cited by
The IL-17 Family of Cytokines in Health and Disease
McGeachy, M. J., Cua, D. J., & Gaffen, S. L. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.021 · Cited by 1,443
Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity
Brestoff, J. R., Kim, B. S., Saenz, S. A., Stine, R. R., Monticelli, L. A., Sonnenberg, G. F., Thome, J. J., Farber, D. L., Lutfy, K., Seale, P., et al. (2015) · Nature · doi:10.1038/nature14115 · Cited by 968
Regulation of metabolism by the innate immune system
Lackey, D. E., & Olefsky, J. M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.189 · Cited by 667
Interleukin-33 in tissue homeostasis, injury, and inflammation
Molofsky, A. B., Savage, A. K., & Locksley, R. M. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.006 · Cited by 638
Self-citationInnate lymphoid cells in the initiation, regulation and resolution of inflammation
Sonnenberg, G. F., & Artis, D. (2015) · Nature Medicine · doi:10.1038/nm.3892 · Cited by 503
Metadata
- Authors
- Hams, E., Locksley, R. M., McKenzie, A. N. J., & Fallon, P. G.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-12-01
- Volume
- 191
- Issue
- 11
- Pages
- 5349-5353
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2122240592
- Cited by
- 232
- References
- 5
- FWCI
- 15.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Hams, E., Locksley, R. M., McKenzie, A. N. J., & Fallon, P. G. (2013). Cutting Edge: IL-25 Elicits Innate Lymphoid Type 2 and Type II NKT Cells That Regulate Obesity in Mice. The Journal of Immunology. https://doi.org/10.4049/jimmunol.1301176
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