CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+T cells in diabetic autoimmunity
- Author
- Neetu Srivastava, Hao Hu, Orion J. Peterson, Anthony N. Vomund, Marta Stremska, Mohammad Zaman, Shilpi Giri, Tiandao Li, Cheryl F. Lichti, Pavel N. Zakharov, Bo Zhang, Nada A. Abumrad, Yi-Guang Chen, Kodi Ravichandran (UGent) , Emil R. Unanue and Xiaoxiao Wan
- Organization
- Abstract
- The pancreatic islet microenvironment is highly oxidative, rendering b cells vulnerable to autoinflammatory insults. Here, we examined the role of islet resident macrophages in the autoimmune attack that initiates type 1 diabetes. Islet macrophages highly expressed CXCL16, a chemokine and scavenger receptor for oxidized low-density lipoproteins (OxLDLs), regardless of autoimmune predisposition. Deletion of Cxcl16 in nonobese diabetic (NOD) mice suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency impaired clearance of OxLDL by islet macrophages, leading to OxLDL accumulation in pancreatic islets and a substantial reduction in intra-islet transitory (Texint) int ) CD8+ + T cells displaying proliferative and effector signatures. Texint int cells were vulnerable to oxidative stress and diminished by ferroptosis; PD-1 blockade rescued this population and reversed diabetes resistance in NOD.Cxcl16-/-- /- mice. Thus, OxLDL scavenging in pancreatic islets inadvertently promotes differentiation of pathogenic CD8+ + T cells, presenting a paradigm wherein tissue homeostasis processes can facilitate autoimmune pathogenesis in predisposed individuals.
- Keywords
- LOW-DENSITY-LIPOPROTEIN, AUTOREACTIVE T-CELLS, ENZYME GENE-EXPRESSION, PANCREATIC-ISLETS, BETA-CELLS, FERROPTOSIS, RECEPTOR, RESIDENT, CD36, PROGRESSION
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Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01J739BFMW7822MQ1KBSQ1C2P0
- MLA
- Srivastava, Neetu, et al. “CXCL16-Dependent Scavenging of Oxidized Lipids by Islet Macrophages Promotes Differentiation of Pathogenic CD8+T Cells in Diabetic Autoimmunity.” IMMUNITY, vol. 57, no. 7, 2024, pp. 1629-1647.e8, doi:10.1016/j.immuni.2024.04.017.
- APA
- Srivastava, N., Hu, H., Peterson, O. J., Vomund, A. N., Stremska, M., Zaman, M., … Wan, X. (2024). CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+T cells in diabetic autoimmunity. IMMUNITY, 57(7), 1629-1647.e8. https://doi.org/10.1016/j.immuni.2024.04.017
- Chicago author-date
- Srivastava, Neetu, Hao Hu, Orion J. Peterson, Anthony N. Vomund, Marta Stremska, Mohammad Zaman, Shilpi Giri, et al. 2024. “CXCL16-Dependent Scavenging of Oxidized Lipids by Islet Macrophages Promotes Differentiation of Pathogenic CD8+T Cells in Diabetic Autoimmunity.” IMMUNITY 57 (7): 1629-1647.e8. https://doi.org/10.1016/j.immuni.2024.04.017.
- Chicago author-date (all authors)
- Srivastava, Neetu, Hao Hu, Orion J. Peterson, Anthony N. Vomund, Marta Stremska, Mohammad Zaman, Shilpi Giri, Tiandao Li, Cheryl F. Lichti, Pavel N. Zakharov, Bo Zhang, Nada A. Abumrad, Yi-Guang Chen, Kodi Ravichandran, Emil R. Unanue, and Xiaoxiao Wan. 2024. “CXCL16-Dependent Scavenging of Oxidized Lipids by Islet Macrophages Promotes Differentiation of Pathogenic CD8+T Cells in Diabetic Autoimmunity.” IMMUNITY 57 (7): 1629-1647.e8. doi:10.1016/j.immuni.2024.04.017.
- Vancouver
- 1.Srivastava N, Hu H, Peterson OJ, Vomund AN, Stremska M, Zaman M, et al. CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+T cells in diabetic autoimmunity. IMMUNITY. 2024;57(7):1629-1647.e8.
- IEEE
- [1]N. Srivastava et al., “CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+T cells in diabetic autoimmunity,” IMMUNITY, vol. 57, no. 7, pp. 1629-1647.e8, 2024.
@article{01J739BFMW7822MQ1KBSQ1C2P0,
abstract = {{The pancreatic islet microenvironment is highly oxidative, rendering b cells vulnerable to autoinflammatory insults. Here, we examined the role of islet resident macrophages in the autoimmune attack that initiates type 1 diabetes. Islet macrophages highly expressed CXCL16, a chemokine and scavenger receptor for oxidized low-density lipoproteins (OxLDLs), regardless of autoimmune predisposition. Deletion of Cxcl16 in nonobese diabetic (NOD) mice suppressed the development of autoimmune diabetes. Mechanistically, Cxcl16 deficiency impaired clearance of OxLDL by islet macrophages, leading to OxLDL accumulation in pancreatic islets and a substantial reduction in intra-islet transitory (Texint) int ) CD8+ + T cells displaying proliferative and effector signatures. Texint int cells were vulnerable to oxidative stress and diminished by ferroptosis; PD-1 blockade rescued this population and reversed diabetes resistance in NOD.Cxcl16-/-- /- mice. Thus, OxLDL scavenging in pancreatic islets inadvertently promotes differentiation of pathogenic CD8+ + T cells, presenting a paradigm wherein tissue homeostasis processes can facilitate autoimmune pathogenesis in predisposed individuals.}},
author = {{Srivastava, Neetu and Hu, Hao and Peterson, Orion J. and Vomund, Anthony N. and Stremska, Marta and Zaman, Mohammad and Giri, Shilpi and Li, Tiandao and Lichti, Cheryl F. and Zakharov, Pavel N. and Zhang, Bo and Abumrad, Nada A. and Chen, Yi-Guang and Ravichandran, Kodi and Unanue, Emil R. and Wan, Xiaoxiao}},
issn = {{1074-7613}},
journal = {{IMMUNITY}},
keywords = {{LOW-DENSITY-LIPOPROTEIN,AUTOREACTIVE T-CELLS,ENZYME GENE-EXPRESSION,PANCREATIC-ISLETS,BETA-CELLS,FERROPTOSIS,RECEPTOR,RESIDENT,CD36,PROGRESSION}},
language = {{eng}},
number = {{7}},
pages = {{1629--1647.e8}},
title = {{CXCL16-dependent scavenging of oxidized lipids by islet macrophages promotes differentiation of pathogenic CD8+T cells in diabetic autoimmunity}},
url = {{http://doi.org/10.1016/j.immuni.2024.04.017}},
volume = {{57}},
year = {{2024}},
}
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