Transcription factor Tox2 is required for metabolic adaptation and tissue residency of ILC3 in the gut.
Group 3 innate lymphoid cells (ILC3) are the major subset of gut-resident ILC with essential roles in infections and tissue repair, but how they adapt to the gut environment to maintain tissue residency is unclear. We report that Tox2 is critical for gut ILC3 maintenance and function. Gut ILC3 highly expressed Tox2, and depletion of Tox2 markedly decreased ILC3 in gut but not at central sites, resulting in defective control of Citrobacter rodentium infection. Single-cell transcriptional profiling revealed decreased expression of Hexokinase-2 in Tox2-deficient gut ILC3. Consistent with the requirement for hexokinases in glycolysis, Tox2-/- ILC3 displayed decreased ability to utilize glycolysis for protein translation. Ectopic expression of Hexokinase-2 rescued Tox2-/- gut ILC3 defects. Hypoxia and interleukin (IL)-17A each induced Tox2 expression in ILC3, suggesting a mechanism by which ILC3 adjusts to fluctuating environments by programming glycolytic metabolism. Our results reveal the requirement for Tox2 to support the metabolic adaptation of ILC3 within the gastrointestinal tract.
Pubmed ID: 38677292
Research resources used in this publication
Additional research tools detected in this publication
None foundAntibodies used in this publication
- IFN gamma Monoclonal Antibody (XMG1.2), PE-Cyanine7, eBioscience (RRID:AB_469680)
- CD4 Monoclonal Antibody (GK1.5), Biotin, eBioscience (RRID:AB_466326)
- CD45R (B220) Monoclonal Antibody (RA3-6B2), APC, eBioscience (RRID:AB_469395)
- IL-17A Monoclonal Antibody (eBio17B7), PE-Cyanine7, eBioscience (RRID:AB_10732356)
- IL-22 Monoclonal Antibody (1H8PWSR), PE, eBioscience (RRID:AB_10597428)
- Bcl-6 (RRID:AB_10717126)
- Recombinant Anti-Hexokinase II antibody [EPR20839] (RRID:AB_2904621)
- Recombinant Anti-Hexokinase 1 antibody [EPR10134(B)] - Mitochondrial Outer Membrane Marker (RRID:AB_2920536)
- Bcl-6 (RRID:AB_10716202)
- HIF-1α (D1S7W) XP® Rabbit mAb (PE Conjugate) (RRID:AB_2799565)
- EOMES Monoclonal Antibody (Dan11mag), Alexa Fluor™ 488, eBioscience (RRID:AB_10854265)
- Gata-3 Monoclonal Antibody (TWAJ), eFluor™ 660, eBioscience (RRID:AB_10596663)
- Brilliant Violet 605(TM) anti-mouse CD19 (RRID:AB_2563067)
- Gata-3 Monoclonal Antibody (TWAJ), PE, eBioscience (RRID:AB_1963600)
- T-bet Monoclonal Antibody (eBio4B10 (4B10)), eFluor™ 450, eBioscience (RRID:AB_2784727)
- PE-CF594 Mouse Anti-Mouse RORγt Clone Q31-378 (RRID:AB_2651150)
- APC/Cyanine7 anti-mouse/human CD45R/B220 (RRID:AB_313007)
- CD5 (RRID:AB_2738061)
- CD49b (Integrin alpha 2) Monoclonal Antibody (DX5), APC-eFluor™ 780, eBioscience (RRID:AB_11218895)
- APC anti-mouse CD49a (RRID:AB_2562253)
- PE/Cyanine7 anti-mouse CD196 (CCR6) (RRID:AB_2072798)
- CD3e Monoclonal Antibody (145-2C11), eFluor™ 450, eBioscience (RRID:AB_10735092)
- Brilliant Violet 605(TM) anti-mouse CD3 (RRID:AB_2562039)
- FITC anti-mouse CD25 (RRID:AB_961212)
- Integrin alpha 4 beta 7 (LPAM-1) Monoclonal Antibody (DATK32 (DATK-32)), PE, eBioscience (RRID:AB_657803)
- Integrin alpha 4 beta 7 (LPAM-1) Monoclonal Antibody (DATK32 (DATK-32)), PerCP-eFluor™ 710, eBioscience (RRID:AB_2573793)
- CD135 (FLT3) (RRID:AB_2737639)
- Pacific Blue(TM) anti-mouse CD5 (RRID:AB_2813916)
- Ly-6A/E (Sca-1) Monoclonal Antibody (D7), PerCP-Cyanine5.5, eBioscience (RRID:AB_914372)
- NK1.1 Monoclonal Antibody (PK136), PE-Cyanine7, eBioscience (RRID:AB_469665)
- NK1.1 Monoclonal Antibody (PK136), APC-eFluor™ 780, eBioscience (RRID:AB_2735070)
- Brilliant Violet 605(TM) anti-mouse CD90.2 (Thy1.2) (RRID:AB_2650924)
- Alexa Fluor(R) 700 anti-mouse CD90.2 (Thy1.2) (RRID:AB_2566740)
- CD197 (CCR7) Monoclonal Antibody (3D12), APC, eBioscience (RRID:AB_1272036)
- CD335 (NKp46) Monoclonal Antibody (29A1.4), PerCP-eFluor™ 710, eBioscience (RRID:AB_1834441)
- CD45.1 Monoclonal Antibody (A20), PerCP-Cyanine5.5, eBioscience (RRID:AB_1107003)
- CD45.2 Monoclonal Antibody (104), PE, eBioscience (RRID:AB_465678)
- PerCP/Cyanine5.5 anti-mouse CD45.2 (RRID:AB_893350)
- CD45.1 Monoclonal Antibody (A20), PE-eFluor™ 610, eBioscience (RRID:AB_2574560)
- CD45.2 Monoclonal Antibody (104), eFluor™ 450, eBioscience (RRID:AB_11042125)
- FITC anti-mouse CD326 (Ep-CAM) (RRID:AB_1134106)
- NK1.1 Monoclonal Antibody (PK136), Super Bright™ 780, eBioscience (RRID:AB_2744923)
- PerCP/Cyanine5.5 anti-mouse CD326 (Ep-CAM) (RRID:AB_2246499)
- Brilliant Violet 785(TM) anti-mouse/human KLRG1 (MAFA) (RRID:AB_2629749)
- APC/Cyanine7 anti-mouse CD326 (Ep-CAM) (RRID:AB_2098648)
- CD127 Monoclonal Antibody (A7R34), APC, eBioscience (RRID:AB_469435)
- APC/Cyanine7 anti-mouse CD335 (NKp46) (RRID:AB_2876479)
- CD117 (c-Kit) Monoclonal Antibody (2B8), PE-Cyanine7, eBioscience (RRID:AB_469644)
- CD117 (c-Kit) Monoclonal Antibody (ACK2), Alexa Fluor™ 700, eBioscience (RRID:AB_657583)
- NOT AN ANTIBODY Streptavidin APC-eFluor 780 100 ug (RRID:AB_10366688)
- CD335 (NKp46) Monoclonal Antibody (29A1.4), PE, eBioscience (RRID:AB_1210743)
- KLRG1 Monoclonal Antibody (2F1), APC-eFluor™ 780, eBioscience (RRID:AB_2573988)
- CD5 Monoclonal Antibody (53-7.3), Biotin, eBioscience (RRID:AB_466339)
- TCR beta Monoclonal Antibody (H57-597), Biotin, eBioscience (RRID:AB_466819)
- TCR gamma/delta Monoclonal Antibody (eBioGL3 (GL-3, GL3)), Biotin, eBioscience (RRID:AB_466668)
- CD8 beta Monoclonal Antibody (CT-CD8b), Biotin (RRID:AB_2539229)
- CD8a Monoclonal Antibody (53-6.7), Biotin, eBioscience (RRID:AB_466346)
- CD11c Monoclonal Antibody (N418), Biotin, eBioscience (RRID:AB_466363)
- Ly-6G/Ly-6C Monoclonal Antibody (RB6-8C5), Biotin, eBioscience (RRID:AB_466800)
- CD11b Monoclonal Antibody (M1/70), Biotin, eBioscience (RRID:AB_466359)
- CD19 Monoclonal Antibody (eBio1D3 (1D3)), Biotin, eBioscience (RRID:AB_657656)
- CD3e Monoclonal Antibody (eBio500A2 (500A2)), Biotin, eBioscience (RRID:AB_842774)
- NK1.1 Monoclonal Antibody (PK136), Biotin, eBioscience (RRID:AB_466804)
- CD45R (B220) Monoclonal Antibody (RA3-6B2), Biotin, eBioscience (RRID:AB_466449)
- Ly-6D Antibody, anti-mouse, Biotin, REAfinity™ (RRID:AB_2726990)
- TER-119 Monoclonal Antibody (TER-119), Biotin, eBioscience (RRID:AB_466797)
Associated grants
- Agency: NCI NIH HHS, United States
Id: HHSN261201500003C - Agency: NCI NIH HHS, United States
Id: HHSN261201500003I - Agency: Intramural NIH HHS, United States
Id: Z99 CA999999 - Agency: Intramural NIH HHS, United States
Id: ZIA BC011633
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This is a list of tools and resources that we have found mentioned in this publication.
IFN gamma Monoclonal Antibody (XMG1.2), PE-Cyanine7, eBioscience (antibody)
RRID:AB_469680
This monoclonal targets IFN gamma
View all literature mentionsCD4 Monoclonal Antibody (GK1.5), Biotin, eBioscience (antibody)
RRID:AB_466326
This monoclonal targets CD4
View all literature mentionsCD45R (B220) Monoclonal Antibody (RA3-6B2), APC, eBioscience (antibody)
RRID:AB_469395
This monoclonal targets CD45R (B220)
View all literature mentionsIL-17A Monoclonal Antibody (eBio17B7), PE-Cyanine7, eBioscience (antibody)
RRID:AB_10732356
This monoclonal targets IL-17A
View all literature mentionsIL-22 Monoclonal Antibody (1H8PWSR), PE, eBioscience (antibody)
RRID:AB_10597428
This monoclonal targets IL-22
View all literature mentionsRecombinant Anti-Hexokinase II antibody [EPR20839] (antibody)
RRID:AB_2904621
This recombinant monoclonal targets Hexokinase II
View all literature mentionsRecombinant Anti-Hexokinase 1 antibody [EPR10134(B)] - Mitochondrial Outer Membrane Marker (antibody)
RRID:AB_2920536
This recombinant monoclonal targets Human Hexokinase 1
View all literature mentionsHIF-1α (D1S7W) XP® Rabbit mAb (PE Conjugate) (antibody)
RRID:AB_2799565
This monoclonal targets HIF1A
View all literature mentionsEOMES Monoclonal Antibody (Dan11mag), Alexa Fluor™ 488, eBioscience (antibody)
RRID:AB_10854265
This monoclonal targets EOMES
View all literature mentionsGata-3 Monoclonal Antibody (TWAJ), eFluor™ 660, eBioscience (antibody)
RRID:AB_10596663
This monoclonal targets Gata-3
View all literature mentionsBrilliant Violet 605(TM) anti-mouse CD19 (antibody)
RRID:AB_2563067
This monoclonal targets CD19
View all literature mentionsGata-3 Monoclonal Antibody (TWAJ), PE, eBioscience (antibody)
RRID:AB_1963600
This monoclonal targets Gata-3
View all literature mentionsT-bet Monoclonal Antibody (eBio4B10 (4B10)), eFluor™ 450, eBioscience (antibody)
RRID:AB_2784727
This monoclonal targets T-bet
View all literature mentionsPE-CF594 Mouse Anti-Mouse RORγt Clone Q31-378 (antibody)
RRID:AB_2651150
This monoclonal targets Mouse RORγt
View all literature mentionsAPC/Cyanine7 anti-mouse/human CD45R/B220 (antibody)
RRID:AB_313007
This monoclonal targets CD45R
View all literature mentionsCD49b (Integrin alpha 2) Monoclonal Antibody (DX5), APC-eFluor™ 780, eBioscience (antibody)
RRID:AB_11218895
This monoclonal targets CD49b (Integrin alpha 2)
View all literature mentionsAPC anti-mouse CD49a (antibody)
RRID:AB_2562253
This monoclonal targets CD49a
View all literature mentionsPE/Cyanine7 anti-mouse CD196 (CCR6) (antibody)
RRID:AB_2072798
This monoclonal targets CD196
View all literature mentionsCD3e Monoclonal Antibody (145-2C11), eFluor™ 450, eBioscience (antibody)
RRID:AB_10735092
This monoclonal targets CD3e
View all literature mentionsBrilliant Violet 605(TM) anti-mouse CD3 (antibody)
RRID:AB_2562039
This monoclonal targets CD3
View all literature mentionsFITC anti-mouse CD25 (antibody)
RRID:AB_961212
This monoclonal targets CD25
View all literature mentionsIntegrin alpha 4 beta 7 (LPAM-1) Monoclonal Antibody (DATK32 (DATK-32)), PE, eBioscience (antibody)
RRID:AB_657803
This monoclonal targets Integrin alpha 4 beta 7 (LPAM-1)
View all literature mentionsIntegrin alpha 4 beta 7 (LPAM-1) Monoclonal Antibody (DATK32 (DATK-32)), PerCP-eFluor™ 710, eBioscience (antibody)
RRID:AB_2573793
This monoclonal targets Integrin alpha 4 beta 7 (LPAM-1)
View all literature mentionsCD135 (FLT3) (antibody)
RRID:AB_2737639
This monoclonal targets CD135 (FLT3)
View all literature mentionsPacific Blue(TM) anti-mouse CD5 (antibody)
RRID:AB_2813916
This monoclonal targets CD5
View all literature mentionsLy-6A/E (Sca-1) Monoclonal Antibody (D7), PerCP-Cyanine5.5, eBioscience (antibody)
RRID:AB_914372
This monoclonal targets Ly-6A/E (Sca-1)
View all literature mentionsNK1.1 Monoclonal Antibody (PK136), PE-Cyanine7, eBioscience (antibody)
RRID:AB_469665
This monoclonal targets NK1.1
View all literature mentionsNK1.1 Monoclonal Antibody (PK136), APC-eFluor™ 780, eBioscience (antibody)
RRID:AB_2735070
This monoclonal targets NK1.1
View all literature mentionsBrilliant Violet 605(TM) anti-mouse CD90.2 (Thy1.2) (antibody)
RRID:AB_2650924
This monoclonal targets CD90.2
View all literature mentionsAlexa Fluor(R) 700 anti-mouse CD90.2 (Thy1.2) (antibody)
RRID:AB_2566740
This monoclonal targets CD90.2
View all literature mentionsCD197 (CCR7) Monoclonal Antibody (3D12), APC, eBioscience (antibody)
RRID:AB_1272036
This monoclonal targets CD197 (CCR7)
View all literature mentionsCD335 (NKp46) Monoclonal Antibody (29A1.4), PerCP-eFluor™ 710, eBioscience (antibody)
RRID:AB_1834441
This monoclonal targets CD335 (NKp46)
View all literature mentionsCD45.1 Monoclonal Antibody (A20), PerCP-Cyanine5.5, eBioscience (antibody)
RRID:AB_1107003
This monoclonal targets CD45.1
View all literature mentionsCD45.2 Monoclonal Antibody (104), PE, eBioscience (antibody)
RRID:AB_465678
This monoclonal targets CD45.2
View all literature mentionsPerCP/Cyanine5.5 anti-mouse CD45.2 (antibody)
RRID:AB_893350
This monoclonal targets CD45.2
View all literature mentionsCD45.1 Monoclonal Antibody (A20), PE-eFluor™ 610, eBioscience (antibody)
RRID:AB_2574560
This monoclonal targets CD45.1
View all literature mentionsCD45.2 Monoclonal Antibody (104), eFluor™ 450, eBioscience (antibody)
RRID:AB_11042125
This monoclonal targets CD45.2
View all literature mentionsFITC anti-mouse CD326 (Ep-CAM) (antibody)
RRID:AB_1134106
This monoclonal targets CD326
View all literature mentionsNK1.1 Monoclonal Antibody (PK136), Super Bright™ 780, eBioscience (antibody)
RRID:AB_2744923
This monoclonal targets NK1.1
View all literature mentionsPerCP/Cyanine5.5 anti-mouse CD326 (Ep-CAM) (antibody)
RRID:AB_2246499
This monoclonal targets CD326
View all literature mentionsBrilliant Violet 785(TM) anti-mouse/human KLRG1 (MAFA) (antibody)
RRID:AB_2629749
This monoclonal targets KLRG1
View all literature mentionsAPC/Cyanine7 anti-mouse CD326 (Ep-CAM) (antibody)
RRID:AB_2098648
This monoclonal targets CD326
View all literature mentionsCD127 Monoclonal Antibody (A7R34), APC, eBioscience (antibody)
RRID:AB_469435
This monoclonal targets CD127
View all literature mentionsAPC/Cyanine7 anti-mouse CD335 (NKp46) (antibody)
RRID:AB_2876479
This monoclonal targets CD335
View all literature mentionsCD117 (c-Kit) Monoclonal Antibody (2B8), PE-Cyanine7, eBioscience (antibody)
RRID:AB_469644
This monoclonal targets CD117 (c-Kit)
View all literature mentionsCD117 (c-Kit) Monoclonal Antibody (ACK2), Alexa Fluor™ 700, eBioscience (antibody)
RRID:AB_657583
This monoclonal targets CD117 (c-Kit)
View all literature mentionsNOT AN ANTIBODY Streptavidin APC-eFluor 780 100 ug (antibody)
RRID:AB_10366688
This unknown targets Biotin
View all literature mentionsCD335 (NKp46) Monoclonal Antibody (29A1.4), PE, eBioscience (antibody)
RRID:AB_1210743
This monoclonal targets CD335 (NKp46)
View all literature mentionsKLRG1 Monoclonal Antibody (2F1), APC-eFluor™ 780, eBioscience (antibody)
RRID:AB_2573988
This monoclonal targets KLRG1
View all literature mentionsCD5 Monoclonal Antibody (53-7.3), Biotin, eBioscience (antibody)
RRID:AB_466339
This monoclonal targets CD5
View all literature mentionsTCR beta Monoclonal Antibody (H57-597), Biotin, eBioscience (antibody)
RRID:AB_466819
This monoclonal targets TCR beta
View all literature mentionsTCR gamma/delta Monoclonal Antibody (eBioGL3 (GL-3, GL3)), Biotin, eBioscience (antibody)
RRID:AB_466668
This monoclonal targets TCR gamma/delta
View all literature mentionsCD8 beta Monoclonal Antibody (CT-CD8b), Biotin (antibody)
RRID:AB_2539229
This monoclonal targets CD8 beta
View all literature mentionsCD8a Monoclonal Antibody (53-6.7), Biotin, eBioscience (antibody)
RRID:AB_466346
This monoclonal targets CD8a
View all literature mentionsCD11c Monoclonal Antibody (N418), Biotin, eBioscience (antibody)
RRID:AB_466363
This monoclonal targets CD11c
View all literature mentionsLy-6G/Ly-6C Monoclonal Antibody (RB6-8C5), Biotin, eBioscience (antibody)
RRID:AB_466800
This monoclonal targets Ly-6G/Ly-6C
View all literature mentionsCD11b Monoclonal Antibody (M1/70), Biotin, eBioscience (antibody)
RRID:AB_466359
This monoclonal targets CD11b
View all literature mentionsCD19 Monoclonal Antibody (eBio1D3 (1D3)), Biotin, eBioscience (antibody)
RRID:AB_657656
This monoclonal targets CD19
View all literature mentionsCD3e Monoclonal Antibody (eBio500A2 (500A2)), Biotin, eBioscience (antibody)
RRID:AB_842774
This monoclonal targets CD3e
View all literature mentionsNK1.1 Monoclonal Antibody (PK136), Biotin, eBioscience (antibody)
RRID:AB_466804
This monoclonal targets NK1.1
View all literature mentionsCD45R (B220) Monoclonal Antibody (RA3-6B2), Biotin, eBioscience (antibody)
RRID:AB_466449
This monoclonal targets CD45R (B220)
View all literature mentionsLy-6D Antibody, anti-mouse, Biotin, REAfinity™ (antibody)
RRID:AB_2726990
This recombinant monoclonal targets Ly-6D
View all literature mentionsTER-119 Monoclonal Antibody (TER-119), Biotin, eBioscience (antibody)
RRID:AB_466797
This monoclonal targets TER-119
View all literature mentionsB6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J (organism)
RRID:IMSR_JAX:006148
Mus musculus with name B6.129X1-Gt(ROSA)26Sortm1(EYFP)Cos/J from IMSR.
View all literature mentionsB6.129-Hif1atm3Rsjo/J (organism)
RRID:IMSR_JAX:007561
Mus musculus with name B6.129-Hif1atm3Rsjo/J from IMSR.
View all literature mentions
