期刊
IMMUNITY
卷 55, 期 6, 页码 1032-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2022.05.013
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类别
资金
- Italian Foundation for Cancer Research [AIRC 19903]
- Telethon [GGP17094]
- Prin [2017BZEREZ]
- Italian Multiple Sclerosis Foundation [FISM 2019/R-single/012]
- US National Institutes of Health [R01AI150297]
This study identifies a previously unrecognized metabolic communication pathway, in which cDC1 cells extend their immunoregulatory capacity to cDC2 through the production of L-kynurenine. This finding has potential therapeutic implications in treating autoimmune demyelinating diseases.
Conventional dendritic cells (cDCs), cDC1 and cDC2, act both to initiate immunity and maintain self-tolerance. The tryptophan metabolic enzyme indoleamine 2,3-dioxygenase 1 (IDO1) is used by cDCs in maintaining tolerance, but its role in different subsets remains unclear At homeostasis, only mature CCR7(+) cDC1 expressed IDO1 that was dependent on IRF8. Lipopolysaccharide treatment induced maturation and IDO1-dependent tolerogenic activity in isolated immature cDC1, but not isolated cDC2. However, both human and mouse cDC2 could induce IDO1 and acquire tolerogenic function when co-cultured with mature cDC1 through the action of cDC1-derived L-kynurenine. Accordingly, cDC1-specific inactivation of IDO1 in vivo exacerbated disease in experimental autoimmune encephalomyelitis. This study identifies a previously unrecognized metabolic communication in which IDO1-expressing cDC1 cells extend their immunoregulatory capacity to the cDC2 subset through their production of tryptophan metabolite L-kynurenine. This metabolic axis represents a potential therapeutic target in treating autoimmune demyelinating diseases.
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