title: Impact of CD1d deficiency on metabolism.
abstract: 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.
authors: Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, United States of America. maya.kotas@gmail.com
authors: Maya E
authors: ME
authors: Kotas
authors: Hui-Young
authors: HY
authors: Lee
authors: Matthew P
authors: MP
authors: Gillum
authors: Charles
authors: C
authors: Annicelli
authors: Blas A
authors: BA
authors: Guigni
authors: Gerald I
authors: GI
authors: Shulman
authors: Ruslan
authors: R
authors: Medzhitov
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000235:genetics / Q000378:metabolism*; D001835:Body Weight; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6 / Q000235:genetics; D002794:Choline / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D018149:Glucose Intolerance; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D055611:Natural Killer T-Cells / Q000378:metabolism; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D010641:Phenotype
chemical_list: D055610:Antigens, CD1d; D000075743:Chemokine CXCL16; D054427:Chemokine CXCL6; C498926:Cxcl16 protein, mouse; D007328:Insulin; D002794:Choline