Indoleamine 2, 3-Dioxygenase Promotes Aryl Hydrocarbon Receptor-Dependent Differentiation Of Regulatory B Cells in Lung Cancer
In: Frontiers in Immunology, Jg. 12 (2021-11-01)
Online
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Zugriff:
Regulatory B cells (Breg) are IL-10 producing subsets of B cells that contribute to immunosuppression in the tumor microenvironment (TME). Breg are elevated in patients with lung cancer; however, the mechanisms underlying Breg development and their function in lung cancer have not been adequately elucidated. Herein, we report a novel role for Indoleamine 2, 3- dioxygenase (IDO), a metabolic enzyme that degrades tryptophan (Trp) and the Trp metabolite L-kynurenine (L-Kyn) in the regulation of Breg differentiation in the lung TME. Using a syngeneic mouse model of lung cancer, we report that Breg frequencies significantly increased during tumor progression in the lung TME and secondary lymphoid organs, while Breg were reduced in tumor-bearing IDO deficient mice (IDO-/-). Trp metabolite L-Kyn promoted Breg differentiationin-vitroin an aryl hydrocarbon receptor (AhR), toll-like receptor-4-myeloid differentiation primary response 88, (TLR4-MyD88) dependent manner. Importantly, using mouse models with conditional deletion of IDO in myeloid-lineage cells, we identified a significant role for immunosuppressive myeloid-derived suppressor cell (MDSC)-associated IDO in modulatingin-vivoandex-vivodifferentiation of Breg. Our studies thus identify Trp metabolism as a therapeutic target to modulate regulatory B cell function during lung cancer progression.
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Indoleamine 2, 3-Dioxygenase Promotes Aryl Hydrocarbon Receptor-Dependent Differentiation Of Regulatory B Cells in Lung Cancer
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Autor/in / Beteiligte Person: | Tousif, Sultan ; Thannickal, Victor J. ; Jackson, Joshua D. ; Hough, Kenneth P. ; Ponnazhagan, Selvarangan ; Strenkowski, John G. ; Wang, Yong ; McCusker, Robert H. ; Athar, Mohammad ; Deshane, Jessy S. |
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Zeitschrift: | Frontiers in Immunology, Jg. 12 (2021-11-01) |
Veröffentlichung: | Frontiers Media S.A., 2021 |
Medientyp: | unknown |
ISSN: | 1664-3224 (print) |
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