B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity.
Nature
; 599(7885): 471-476, 2021 11.
Article
en En
| MEDLINE
| ID: mdl-34732892
ABSTRACT
Small, soluble metabolites not only are essential intermediates in intracellular biochemical processes, but can also influence neighbouring cells when released into the extracellular milieu1-3. Here we identify the metabolite and neurotransmitter GABA as a candidate signalling molecule synthesized and secreted by activated B cells and plasma cells. We show that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages that secrete interleukin-10 and inhibit CD8+ T cell killer function. In mice, B cell deficiency or B cell-specific inactivation of the GABA-generating enzyme GAD67 enhances anti-tumour responses. Our study reveals that, in addition to cytokines and membrane proteins, small metabolites derived from B-lineage cells have immunoregulatory functions, which may be pharmaceutical targets allowing fine-tuning of immune responses.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos B
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Interleucina-10
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Ácido gamma-Aminobutírico
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Macrófagos
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Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Female
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Humans
/
Male
Idioma:
En
Año:
2021
Tipo del documento:
Article