Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients

被引:253
作者
Magalhaes, Isabelle [1 ,2 ,3 ]
Pingris, Karine [1 ,2 ,3 ]
Poitou, Christine [4 ,5 ,6 ]
Bessoles, Stephanie [7 ]
Venteclef, Nicolas [4 ,5 ]
Kiaf, Badr [1 ,2 ,3 ]
Beaudoin, Lucie [1 ,2 ,3 ]
Da Silva, Jennifer [1 ,2 ,3 ]
Allatif, Omran [4 ,5 ,6 ]
Rossjohn, Jamie [8 ,9 ]
Kjer-Nielsen, Lars [10 ]
McCluskey, James [10 ]
Ledoux, Severine [1 ,2 ,3 ,11 ]
Genser, Laurent [4 ,5 ,6 ]
Torcivia, Adriana [12 ]
Soudais, Claire [7 ]
Lantz, Olivier [7 ]
Boitard, Christian [1 ,2 ,3 ,13 ]
Aron-Wisnewsky, Judith [4 ,5 ,6 ]
Larger, Etienne [1 ,2 ,3 ,13 ]
Clement, Karine [4 ,5 ,6 ]
Lehuen, Agnes [1 ,2 ,3 ,13 ]
机构
[1] INSERM, U1016, Inst Cochin, F-75014 Paris, France
[2] CNRS, UMR8104, Paris, France
[3] Univ Paris 05, Sorbonne Paris Cite, Lab Excellence INFLAMEX, Paris, France
[4] Univ Paris 06, Sorbonne Univ, Paris, France
[5] INSERM, U1166, Inst Cardiometab & Nutr ICAN, Paris, France
[6] Hop La Pitie Salpetriere, AP HP, ICAN, Dept Nutr, Paris, France
[7] INSERM, U932, Inst Curie, Paris, France
[8] Monash Univ, ARC, Ctr Excellence Adv Mol Imaging, Clayton, Vic, Australia
[9] Cardiff Univ, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales
[10] Univ Melbourne, Dept Microbiol & Immunol, Peter Doherty Inst Infect & Immun, Parkville, Vic 3052, Australia
[11] Louis Mourier Hosp, AP HP, Serv Explorat Fonct, Ctr Reference Prise Charge Obesite, Paris, France
[12] Hop La Pitie Salpetriere, Dept Chirurg, Paris, France
[13] Cochin Hosp, AP HP, Dept Diabetol, Paris, France
关键词
VITAMIN-B METABOLITES; HUMAN GUT MICROBIOTA; ADIPOSE-TISSUE; NKT CELLS; INFLAMMATION; ACTIVATION; METAGENOME; MR1; DECREASE; WOMEN;
D O I
10.1172/JCI78941
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Obesity and type 2 diabetes (T2D) are associated with low-grade inflammation, activation of immune cells, and alterations of the gut microbiota. Mucosal-associated invariant T (MAIT) cells, which are innate-like T cells that recognize bacterial ligands, are present in blood and enriched in mucosal and inflamed tissues. Here, we analyzed MAIT cells in the blood and adipose tissues of patients with T2D and/or severe obesity. We determined that circulating MAIT cell frequency was dramatically decreased in both patient groups, and this population was even undetectable in some obese patients. Moreover, in both patient groups, circulating MAIT cells displayed an activated phenotype that was associated with elevated Th1 and Th17 cytokine production. In obese patients, MAIT cells were more abundant in adipose tissue than in the blood and exhibited a striking IL-17 profile. Bariatric surgery in obese patients not only improved their metabolic parameters but also increased circulating MAIT cell frequency at 3 months after surgery. Similarly, cytokine production by blood MAIT cells was strongly decreased after surgery. This study reveals profound MAIT cell abnormalities in patients harboring metabolic disorders, suggesting their potential role in these pathologies.
引用
收藏
页码:1752 / 1762
页数:11
相关论文
共 40 条
  • [1] Association of Adipose Tissue and Liver Fibrosis With Tissue Stiffness in Morbid Obesity: Links With Diabetes and BMI Loss After Gastric Bypass
    Abdennour, Meriem
    Reggio, Sophie
    Le Naour, Gilles
    Liu, Yuejun
    Poitou, Christine
    Aron-Wisnewsky, Judith
    Charlotte, Frederic
    Bouillot, Jean-Luc
    Torcivia, Adriana
    Sasso, Magali
    Miette, Veronique
    Zucker, Jean-Daniel
    Bedossa, Pierre
    Tordjman, Joan
    Clement, Karine
    [J]. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2014, 99 (03) : 898 - 907
  • [2] Analysis of CD161 expression on human CD8+ T cells defines a distinct functional subset with tissue-homing properties
    Billerbeck, Eva
    Kang, Yu-Hoi
    Walker, Lucy
    Lockstone, Helen
    Grafmueller, Stefanie
    Fleming, Vicki
    Flint, Jonathan
    Willberg, Chris B.
    Bengsch, Bertram
    Seigel, Bianca
    Ramamurthy, Narayan
    Zitzmann, Nicole
    Barnes, Eleanor J.
    Thevanayagam, Jonarthan
    Bhagwanani, Anisha
    Leslie, Alasdair
    Oo, Ye H.
    Kollnberger, Simon
    Bowness, Paul
    Drognitz, Oliver
    Adams, David H.
    Blum, Hubert E.
    Thimme, Robert
    Klenerman, Paul
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (07) : 3006 - 3011
  • [3] MAITs, MR1 and vitamin B metabolites
    Birkinshaw, Richard W.
    Kjer-Nielsen, Lars
    Eckle, Sidonia B. G.
    McCluskey, James
    Rossjohn, Jamie
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2014, 26 : 7 - 13
  • [4] Metagenome and metabolism: the tissue microbiota hypothesis
    Burcelin, Remy
    Serino, Matteo
    Chabo, Chantal
    Garidou, Lucile
    Pomie, Celine
    Courtney, Michael
    Amar, Jacques
    Bouloumie, Anne
    [J]. DIABETES OBESITY & METABOLISM, 2013, 15 : 61 - 70
  • [5] T-cell activation by transitory neo-antigens derived from distinct microbial pathways
    Corbett, Alexandra J.
    Eckle, Sidonia B. G.
    Birkinshaw, Richard W.
    Liu, Ligong
    Patel, Onisha
    Mahony, Jennifer
    Chen, Zhenjun
    Reantragoon, Rangsima
    Meehan, Bronwyn
    Cao, Hanwei
    Williamson, Nicholas A.
    Strugnell, Richard A.
    Van Sinderen, Douwe
    Mak, Jeffrey Y. W.
    Fairlie, David P.
    Kjer-Nielsen, Lars
    Rossjohn, Jamie
    McCluskey, James
    [J]. NATURE, 2014, 509 (7500) : 361 - +
  • [6] Early and nonreversible decrease of CD161++/MAIT cells in HIV infection
    Cosgrove, Cormac
    Ussher, James E.
    Rauch, Andri
    Gaertner, Kathleen
    Kurioka, Ayako
    Huehn, Michael H.
    Adelmann, Krista
    Kang, Yu-Hoi
    Fergusson, Joannah R.
    Simmonds, Peter
    Goulder, Philip
    Hansen, Ted H.
    Fox, Julie
    Guenthard, Huldrych F.
    Khanna, Nina
    Powrie, Fiona
    Steel, Alan
    Gazzard, Brian
    Phillips, Rodney E.
    Frater, John
    Uhlig, Holm
    Klenerman, Paul
    [J]. BLOOD, 2013, 121 (06) : 951 - 961
  • [7] Dietary intervention impact on gut microbial gene richness
    Cotillard, Aurelie
    Kennedy, Sean P.
    Kong, Ling Chun
    Prifti, Edi
    Pons, Nicolas
    Le Chatelier, Emmanuelle
    Almeida, Mathieu
    Quinquis, Benoit
    Levenez, Florence
    Galleron, Nathalie
    Gougis, Sophie
    Rizkalla, Salwa
    Batto, Jean-Michel
    Renault, Pierre
    Dore, Joel
    Zucker, Jean-Daniel
    Clement, Karine
    Ehrlich, Stanislav Dusko
    [J]. NATURE, 2013, 500 (7464) : 585 - +
  • [8] T Cell-Derived IL-22 Amplifies IL-1β-Driven Inflammation in Human Adipose Tissue: Relevance to Obesity and Type 2 Diabetes
    Dalmas, Elise
    Venteclef, Nicolas
    Caer, Charles
    Poitou, Christine
    Cremer, Isabelle
    Aron-Wisnewsky, Judith
    Lacroix-Desmazes, Sebastien
    Bayry, Jagadeesh
    Kaveri, Srinivas V.
    Clement, Karine
    Andre, Sebastien
    Guerre-Millo, Michele
    [J]. DIABETES, 2014, 63 (06) : 1966 - 1977
  • [9] Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction
    Dalmas, Elise
    Rouault, Christine
    Abdennour, Meriem
    Rovere, Carole
    Rizkalla, Salwa
    Bar-Hen, Avner
    Nahon, Jean-Louis
    Bouillot, Jean-Luc
    Guerre-Millo, Michele
    Clement, Karine
    Poitou, Christine
    [J]. AMERICAN JOURNAL OF CLINICAL NUTRITION, 2011, 94 (02) : 450 - 458
  • [10] Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells
    Dusseaux, Mathilde
    Martin, Emmanuel
    Serriari, Nacer
    Peguillet, Isabelle
    Premel, Virginie
    Louis, Delphine
    Milder, Maud
    Le Bourhis, Lionel
    Soudais, Claire
    Treiner, Emmanuel
    Lantz, Olivier
    [J]. BLOOD, 2011, 117 (04) : 1250 - 1259