IL-33 activates mTORC1 and modulates glycolytic metabolism in CD8+ T cells
© 2021 John Wiley & Sons Ltd..
Interleukin (IL)-33, a member in the IL-1 family, plays a central role in innate and adaptive immunity; however, how IL-33 mediates cytotoxic T-cell regulation and the downstream signals remain elusive. In this study, we found increased mouse IL-33 expression in CD8+ T cells following cell activation via anti-CD3/CD28 stimulation in vitro or lymphocytic choriomeningitis virus (LCMV) infection in vivo. Our cell adoptive transfer experiment demonstrated that extracellular, but not nuclear, IL-33 contributed to the activation and proliferation of CD8+ , but not CD4+ T effector cells in LCMV infection. Importantly, IL-33 induced mTORC1 activation in CD8+ T cells as evidenced by increased phosphorylated S6 ribosomal protein (p-S6) levels both in vitro and in vivo. Meanwhile, this IL-33-induced CD8+ T-cell activation was suppressed by mTORC1 inhibitors. Furthermore, IL-33 elevated glucose uptake and lactate production in CD8+ T cells in both dose- and time-dependent manners. The results of glycolytic rate assay demonstrated the increased glycolytic capacity of IL-33-treated CD8+ T cells compared with that of control cells. Our mechanistic study further revealed the capacity of IL-33 in promoting the expression of glucose transporter 1 (Glut1) and glycolytic enzymes via mTORC1, leading to accelerated aerobic glucose metabolism Warburg effect and increased effector T-cell activation. Together, our data provide new insights into IL-33-mediated regulation of CD8+ T cells, which might be beneficial for therapeutic strategies of inflammatory and infectious diseases in the future.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:165 |
|---|---|
| Enthalten in: |
Immunology - 165(2022), 1 vom: 19. Jan., Seite 61-73 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liang, Yuejin [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.02.2022 Date Revised 16.07.2022 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/imm.13404 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM329547488 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM329547488 | ||
| 003 | DE-627 | ||
| 005 | 20231225205342.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/imm.13404 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1098.xml |
| 035 | |a (DE-627)NLM329547488 | ||
| 035 | |a (NLM)34411293 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liang, Yuejin |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a IL-33 activates mTORC1 and modulates glycolytic metabolism in CD8+ T cells |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 21.02.2022 | ||
| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 John Wiley & Sons Ltd. | ||
| 520 | |a Interleukin (IL)-33, a member in the IL-1 family, plays a central role in innate and adaptive immunity; however, how IL-33 mediates cytotoxic T-cell regulation and the downstream signals remain elusive. In this study, we found increased mouse IL-33 expression in CD8+ T cells following cell activation via anti-CD3/CD28 stimulation in vitro or lymphocytic choriomeningitis virus (LCMV) infection in vivo. Our cell adoptive transfer experiment demonstrated that extracellular, but not nuclear, IL-33 contributed to the activation and proliferation of CD8+ , but not CD4+ T effector cells in LCMV infection. Importantly, IL-33 induced mTORC1 activation in CD8+ T cells as evidenced by increased phosphorylated S6 ribosomal protein (p-S6) levels both in vitro and in vivo. Meanwhile, this IL-33-induced CD8+ T-cell activation was suppressed by mTORC1 inhibitors. Furthermore, IL-33 elevated glucose uptake and lactate production in CD8+ T cells in both dose- and time-dependent manners. The results of glycolytic rate assay demonstrated the increased glycolytic capacity of IL-33-treated CD8+ T cells compared with that of control cells. Our mechanistic study further revealed the capacity of IL-33 in promoting the expression of glucose transporter 1 (Glut1) and glycolytic enzymes via mTORC1, leading to accelerated aerobic glucose metabolism Warburg effect and increased effector T-cell activation. Together, our data provide new insights into IL-33-mediated regulation of CD8+ T cells, which might be beneficial for therapeutic strategies of inflammatory and infectious diseases in the future | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CD8 | |
| 650 | 4 | |a Glut1 | |
| 650 | 4 | |a IL-33 | |
| 650 | 4 | |a T cells | |
| 650 | 4 | |a glycolytic metabolism | |
| 650 | 4 | |a mTORC1 | |
| 650 | 7 | |a Interleukin-33 |2 NLM | |
| 650 | 7 | |a Lactic Acid |2 NLM | |
| 650 | 7 | |a 33X04XA5AT |2 NLM | |
| 650 | 7 | |a Mechanistic Target of Rapamycin Complex 1 |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Glucose |2 NLM | |
| 650 | 7 | |a IY9XDZ35W2 |2 NLM | |
| 700 | 1 | |a Wang, Xiaofang |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Wenjing |e verfasserin |4 aut | |
| 700 | 1 | |a Yi, Panpan |e verfasserin |4 aut | |
| 700 | 1 | |a Soong, Lynn |e verfasserin |4 aut | |
| 700 | 1 | |a Cong, Yingzi |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Jiyang |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Xuegong |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Jiaren |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Immunology |d 1958 |g 165(2022), 1 vom: 19. Jan., Seite 61-73 |w (DE-627)NLM000004219 |x 1365-2567 |7 nnns |
| 773 | 1 | 8 | |g volume:165 |g year:2022 |g number:1 |g day:19 |g month:01 |g pages:61-73 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/imm.13404 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 165 |j 2022 |e 1 |b 19 |c 01 |h 61-73 | ||