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PMID: 22981538 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Adipose tissue invariant NKT cells protect against diet-induced obesity and metabolic disorder through regulatory cytokine production.

Immunity ·Vol. 37 ·No. 3 ·2012-09-21 ·Pages 574-87

Lynch L, Nowak M, Varghese B, Clark J, Hogan AE, Toxavidis V, Balk SP, O'Shea D, O'Farrelly C, Exley MA

Abstract

Invariant natural killer T (iNKT) cells are evolutionarily conserved innate T cells that influence inflammatory responses. We have shown that iNKT cells, previously thought to be rare in humans, were highly enriched in human and murine adipose tissue, and that as adipose tissue expanded in obesity, iNKT cells were depleted, correlating with proinflammatory macrophage infiltration. iNKT cell numbers were restored in mice and humans after weight loss. Mice lacking iNKT cells had enhanced weight gain, larger adipocytes, fatty livers, and insulin resistance on a high-fat diet. Adoptive transfer of iNKT cells into obese mice or in vivo activation of iNKT cells via their lipid ligand, alpha-galactocylceramide, decreased body fat, triglyceride levels, leptin, and fatty liver and improved insulin sensitivity through anti-inflammatory cytokine production by adipose-derived iNKT cells. This finding highlights the potential of iNKT cell-targeted therapies, previously proven to be safe in humans, in the management of obesity and its consequences.

MeSH Terms
Adipose Tissue/immunology,metabolism Adoptive Transfer Adult Animals Antigens, CD1d/genetics,immunology,metabolism CD11c Antigen/immunology,metabolism Cytokines/immunology,metabolism Diet, High-Fat/adverse effects Female Flow Cytometry Humans Liver/immunology,metabolism Lymphocyte Count Macrophages/immunology,metabolism Male Metabolic Diseases/etiology,immunology,metabolism Mice Mice, Inbred C57BL Mice, Knockout Mice, Obese Middle Aged Natural Killer T-Cells/immunology,metabolism,transplantation Obesity/etiology,immunology,metabolism Spleen/immunology,metabolism Young Adult
Chemicals
Antigens, CD1d CD11c Antigen Cd1d1 protein, mouse Cytokines
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Lynch Lydia
Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. llynch1@bidmc.harvard.edu
Nowak Michael
Varghese Bindu
Clark Justice
Hogan Andrew E
Toxavidis Vasillis
Balk Steven P
O'Shea Donal
O'Farrelly Cliona
Exley Mark A
Conflict of Interest

The other authors have no conflicting financial interests.

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Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1097-4180
DOI
10.1016/j.immuni.2012.06.016
Email
llynch1@bidmc.harvard.edu
Published
2012-09-21
Epub
2012-00-13
Pages
574-87
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC4991771
Subset
IM
Grants
NIDDK NIH HHS · R01 DK066917 · United States
NCI NIH HHS · R21 CA143748 · United States
NCI NIH HHS · R21 CA170194 · United States
NIAID NIH HHS · U19 AI066313 · United States
Corrections
CommentIn
PMID: 22999952
External Links
PubMed source DOI: 10.1016/j.immuni.2012.06.016 PMC Full Text View journal details
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