Impact of CD1d deficiency on metabolism

Invariant natural killer T cells (iNKTs) are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the...

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Bibliographic Details
Published in:PloS one 2011-09, Vol.6 (9), p.e25478-e25478
Main Authors: Kotas, Maya E, Lee, Hui-Young, Gillum, Matthew P, Annicelli, Charles, Guigni, Blas A, Shulman, Gerald I, Medzhitov, Ruslan
Format: Article
Language:English
Subjects:
Animals
Antigens, CD1d - genetics
Antigens, CD1d - metabolism
B cells
Biology
Body Weight
CD1d antigen
Chemokine CXCL16
Chemokine CXCL6 - genetics
Choline
Choline - metabolism
Diet, High-Fat - adverse effects
Disease control
Fatty Liver - metabolism
Fatty Liver - pathology
Feeding
Gene Expression Regulation
Glucose Intolerance
Glucose tolerance
Humans
Immune system
Immunological tolerance
Insulin - metabolism
Insulin resistance
Lipids
Liver
Liver - metabolism
Lymphocytes
Lymphocytes T
Major histocompatibility complex
Male
Medicine
Metabolism
Mice
Natural killer cells
Natural Killer T-Cells - metabolism
Obesity - etiology
Obesity - metabolism
Phenotype
Rodents
Steatosis
T cell receptors
T cells
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Summary:Invariant natural killer T cells (iNKTs) are innate-like T cells that are highly concentrated in the liver and recognize lipids presented on the MHC-like molecule CD1d. Although capable of a myriad of responses, few essential functions have been described for iNKTs. Among the many cell types of the immune system implicated in metabolic control and disease, iNKTs seem ideally poised for such a role, yet little has been done to elucidate such a possible function. We hypothesized that lipid presentation by CD1d could report on metabolic status and engage iNKTs to regulate cellular lipid content through their various effector mechanisms. To test this hypothesis, we examined CD1d deficient mice in a variety of metabolically stressed paradigms including high fat feeding, choline-deficient feeding, fasting, and acute inflammation. CD1d deficiency led to a mild exacerbation of steatosis during high fat or choline-deficient feeding, accompanied by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in Jα18⁻/⁻ mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0025478