Tissue-specific metabolic profile drives iNKT cell function during obesity and liver injury.
Invariant natural killer T (iNKT) cells are a distinct population of lymphocytes characterized by their reactivity to glycolipids presented by CD1d. iNKT cells are found throughout the body, and little is known about their tissue-specific metabolic regulation. Here, we show that splenic and hepatic iNKT cells are metabolically comparable and rely on glycolytic metabolism to support their activation. Deletion of the pyruvate kinase M2 (Pkm2) gene in splenic and hepatic iNKT cells impairs their response to specific stimulation and their ability to mitigate acute liver injury. In contrast, adipose tissue (AT) iNKT cells exhibit a distinctive immunometabolic profile, with AMP-activated protein kinase (AMPK) being necessary for their function. AMPK deficiency impairs AT-iNKT physiology, blocking their capacity to maintain AT homeostasis and their ability to regulate AT inflammation during obesity. Our work deepens our understanding on the tissue-specific immunometabolic regulation of iNKT cells, which directly impacts the course of liver injury and obesity-induced inflammation.
Pubmed ID: 36848232 RIS Download
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- IL-10 (RRID:AB_2738582)
- Rat Anti-CD19 Monoclonal Antibody, FITC Conjugated, Clone 1D3 (RRID:AB_395049)
- Syrian Hamster Anti-CD28 Monoclonal Antibody, Unconjugated, Clone 37.51 (RRID:AB_394763)
- PE anti-mouse CD36 (RRID:AB_389348)
- Rabbit Anti-Human GLUT1 Polyclonal, Unconjugated (RRID:AB_790014)
- APC anti-mouse IFN-gamma (RRID:AB_315404)
- PE/Cyanine7 anti-mouse IL-4 (RRID:AB_10898116)
- APC anti-mouse IL-12/IL-23 p40 (RRID:AB_315370)
- IL-1 beta (Pro-form) Monoclonal Antibody (NJTEN3), PE, eBioscience (RRID:AB_10732630)
- Brilliant Violet 711(TM) anti-mouse TCR beta chain (RRID:AB_2629564)
- Brilliant Violet 421(TM) anti-mouse TCR beta chain (RRID:AB_2562562)
- PerCP/Cyanine5.5 anti-mouse Ly-6G (RRID:AB_1877272)
- PE/Cyanine7 anti-mouse Ly-6C (RRID:AB_1732082)
- PE anti-mouse CD301 (MGL1/MGL2) (RRID:AB_2561961)
- APC anti-mouse CD206 (MMR) (RRID:AB_10900231)
- BV421 Rat Anti-Mouse F4/80 (RRID:AB_2734779)
- PE anti-mouse CD11c (RRID:AB_313777)
- APC/Cyanine7 anti-mouse/human CD11b (RRID:AB_830642)
- Rat Anti-CD45 Monoclonal Antibody, V500 Conjugated, Clone 30-F11 (RRID:AB_10697046)
- CD45 (RRID:AB_394611)
- Brilliant Violet 750(TM) anti-mouse CD45 (RRID:AB_2734155)
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This is a list of tools and resources that we have found mentioned in this publication.
Rat Anti-CD19 Monoclonal Antibody, FITC Conjugated, Clone 1D3 (antibody)
RRID:AB_395049
This monoclonal targets CD19
View all literature mentionsSyrian Hamster Anti-CD28 Monoclonal Antibody, Unconjugated, Clone 37.51 (antibody)
RRID:AB_394763
This monoclonal targets CD28
View all literature mentionsPE anti-mouse CD36 (antibody)
RRID:AB_389348
This monoclonal targets CD36
View all literature mentionsRabbit Anti-Human GLUT1 Polyclonal, Unconjugated (antibody)
RRID:AB_790014
This polyclonal targets Human GLUT1
View all literature mentionsAPC anti-mouse IFN-gamma (antibody)
RRID:AB_315404
This monoclonal targets IFN-gamma
View all literature mentionsPE/Cyanine7 anti-mouse IL-4 (antibody)
RRID:AB_10898116
This monoclonal targets IL-4
View all literature mentionsAPC anti-mouse IL-12/IL-23 p40 (antibody)
RRID:AB_315370
This monoclonal targets IL-12/IL-23 p40
View all literature mentionsIL-1 beta (Pro-form) Monoclonal Antibody (NJTEN3), PE, eBioscience (antibody)
RRID:AB_10732630
This monoclonal targets IL-1 beta (Pro-form)
View all literature mentionsBrilliant Violet 711(TM) anti-mouse TCR beta chain (antibody)
RRID:AB_2629564
This monoclonal targets TCR beta chain
View all literature mentionsBrilliant Violet 421(TM) anti-mouse TCR beta chain (antibody)
RRID:AB_2562562
This monoclonal targets TCR beta chain
View all literature mentionsPerCP/Cyanine5.5 anti-mouse Ly-6G (antibody)
RRID:AB_1877272
This monoclonal targets Ly-6G
View all literature mentionsPE/Cyanine7 anti-mouse Ly-6C (antibody)
RRID:AB_1732082
This monoclonal targets Ly-6C
View all literature mentionsPE anti-mouse CD301 (MGL1/MGL2) (antibody)
RRID:AB_2561961
This monoclonal targets CD301
View all literature mentionsAPC anti-mouse CD206 (MMR) (antibody)
RRID:AB_10900231
This monoclonal targets CD206
View all literature mentionsBV421 Rat Anti-Mouse F4/80 (antibody)
RRID:AB_2734779
This monoclonal targets F4/80
View all literature mentionsPE anti-mouse CD11c (antibody)
RRID:AB_313777
This monoclonal targets CD11c
View all literature mentionsAPC/Cyanine7 anti-mouse/human CD11b (antibody)
RRID:AB_830642
This monoclonal targets CD11b
View all literature mentionsRat Anti-CD45 Monoclonal Antibody, V500 Conjugated, Clone 30-F11 (antibody)
RRID:AB_10697046
This monoclonal targets Rat CD45 V500 Clone 30-F11
View all literature mentionsBrilliant Violet 750(TM) anti-mouse CD45 (antibody)
RRID:AB_2734155
This monoclonal targets CD45
View all literature mentionsB6;129S-Gt(ROSA)26Sortm1(CAG-COX8A/Dendra2)Dcc/J (organism)
RRID:IMSR_JAX:018385
Mus musculus with name B6;129S-Gt(ROSA)26Sortm1(CAG-COX8A/Dendra2)Dcc/J from IMSR.
View all literature mentionsSTOCK Prkaa1tm1.1Sjm/J (organism)
RRID:IMSR_JAX:014141
Mus musculus with name STOCK Prkaa1tm1.1Sjm/J from IMSR.
View all literature mentionsB6;129S-Pkmtm1.1Mgvh/J (organism)
RRID:IMSR_JAX:024048
Mus musculus with name B6;129S-Pkmtm1.1Mgvh/J from IMSR.
View all literature mentionsB6.Cg-Tg(Cd4-cre)1Cwi/BfluJ (organism)
RRID:IMSR_JAX:022071
Mus musculus with name B6.Cg-Tg(Cd4-cre)1Cwi/BfluJ from IMSR.
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