Impact of CD1d Deficiency on Metabolism

被引:69
作者
Kotas, Maya E. [1 ]
Lee, Hui-Young [2 ,4 ]
Gillum, Matthew P. [5 ]
Annicelli, Charles [1 ]
Guigni, Blas A. [2 ]
Shulman, Gerald I. [2 ,3 ,4 ]
Medzhitov, Ruslan [1 ,4 ]
机构
[1] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA
[2] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA
[3] Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA
[4] Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA
[5] Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA
关键词
KILLER T-CELLS; FATTY LIVER-DISEASE; INSULIN-RESISTANCE; NKT CELLS; IMMUNE-SYSTEM; GLUCOSE-INTOLERANCE; INKT CELLS; MICE; OBESITY; ACTIVATION;
D O I
10.1371/journal.pone.0025478
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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, accompained by impaired hepatic glucose tolerance. Surprisingly, however, this phenotype was not observed in J alpha 18(-/-) mice, which are deficient in iNKTs but express CD1d. Thus, CD1d appears to modulate some metabolic functions through an iNKT-independent mechanism.
引用
收藏
页数:17
相关论文
共 55 条
[41]   Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function [J].
Stetson, DB ;
Mohrs, M ;
Reinhardt, RL ;
Baron, JL ;
Wang, ZE ;
Gapin, L ;
Kronenberg, M ;
Locksley, RM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 198 (07) :1069-1076
[42]   PPARγ controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells [J].
Szatmari, Istvan ;
Pap, Attila ;
Ruhl, Ralph ;
Ma, Jiang-Xing ;
Illarionov, Petr A. ;
Besra, Gurdyal S. ;
Rajnavolgyi, Eva ;
Dezso, Balazs ;
Nagy, Laszlo .
JOURNAL OF EXPERIMENTAL MEDICINE, 2006, 203 (10) :2351-2362
[43]  
TO K, 2009, ARTERIOSCLER THROMB
[44]   CD1d-dependent activation of NKT cells aggravates atherosclerosis [J].
Tupin, E ;
Nicoletti, A ;
Elhage, R ;
Rudling, M ;
Ljunggren, HG ;
Hansson, GK ;
Berne, GP .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 199 (03) :417-422
[45]   A semi-invariant Vα10+ T cell antigen receptor defines a population of natural killer T cells with distinct glycolipid antigen-recognition properties [J].
Uldrich, Adam P. ;
Patel, Onisha ;
Cameron, Garth ;
Pellicci, Daniel G. ;
Day, E. Bridie ;
Sullivan, Lucy C. ;
Kyparissoudis, Konstantinos ;
Kjer-Nielsen, Lars ;
Vivian, Julian P. ;
Cao, Benjamin ;
Brooks, Andrew G. ;
Williams, Spencer J. ;
Illarionov, Petr ;
Besra, Gurdyal S. ;
Turner, Stephen J. ;
Porcelli, Steven A. ;
McCluskey, James ;
Smyth, Mark J. ;
Rossjohn, Jamie ;
Godfrey, Dale I. .
NATURE IMMUNOLOGY, 2011, 12 (07) :616-U168
[46]   Cutting Edge: CD28 Engagement Releases Antigen-Activated Invariant NKT Cells from the Inhibitory Effects of PD-1 [J].
Wang, Jianxiong ;
Cheng, Lu ;
Wondimu, Zenebech ;
Swain, Mark ;
Santamaria, Pere ;
Yang, Yang .
JOURNAL OF IMMUNOLOGY, 2009, 182 (11) :6644-6647
[47]   B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies [J].
Winer, Daniel A. ;
Winer, Shawn ;
Shen, Lei ;
Wadia, Persis P. ;
Yantha, Jason ;
Paltser, Geoffrey ;
Tsui, Hubert ;
Wu, Ping ;
Davidson, Matthew G. ;
Alonso, Michael N. ;
Leong, Hwei X. ;
Glassford, Alec ;
Caimol, Maria ;
Kenkel, Justin A. ;
Tedder, Thomas F. ;
McLaughlin, Tracey ;
Miklos, David B. ;
Dosch, H-Michael ;
Engleman, Edgar G. .
NATURE MEDICINE, 2011, 17 (05) :610-U134
[48]   Normalization of obesity-associated insulin resistance through immunotherapy [J].
Winer, Shawn ;
Chan, Yin ;
Paltser, Geoffrey ;
Truong, Dorothy ;
Tsui, Hubert ;
Bahrami, Jasmine ;
Dorfman, Ruslan ;
Wang, Yongqian ;
Zielenski, Julian ;
Mastronardi, Fabrizio ;
Maezawa, Yuko ;
Drucker, Daniel J. ;
Engleman, Edgar ;
Winer, Daniel ;
Dosch, H. -Michael .
NATURE MEDICINE, 2009, 15 (08) :921-U126
[49]   Eosinophils Sustain Adipose Alternatively Activated Macrophages Associated with Glucose Homeostasis [J].
Wu, Davina ;
Molofsky, Ari B. ;
Liang, Hong-Erh ;
Ricardo-Gonzalez, Roberto R. ;
Jouihan, Hani A. ;
Bando, Jennifer K. ;
Chawla, Ajay ;
Locksley, Richard M. .
SCIENCE, 2011, 332 (6026) :243-247
[50]   Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance [J].
Xu, HY ;
Barnes, GT ;
Yang, Q ;
Tan, Q ;
Yang, DS ;
Chou, CJ ;
Sole, J ;
Nichols, A ;
Ross, JS ;
Tartaglia, LA ;
Chen, H .
JOURNAL OF CLINICAL INVESTIGATION, 2003, 112 (12) :1821-1830