The inhibitory receptor Tim-3 fails to suppress IFN-γ production via the NFAT pathway in NK-cell, unlike that in CD4+ T cells.
BMC Immunol
; 22(1): 25, 2021 04 09.
Article
em En
| MEDLINE
| ID: mdl-33832435
ABSTRACT
BACKGROUND:
T cell immunoglobulin and mucin domain-containing-3 (Tim-3) is a negative regulator expressed on T cells, and is also expressed on natural killer (NK) cells. The function of Tim-3 chiefly restricts IFNγ-production in T cells, however, the impact of Tim-3 on NK cell function has not been clearly elucidated.RESULTS:
In this study, we demonstrated down-regulation of Tim-3 expression on NK cells while Tim-3 is upregulated on CD4+ T cells during HIV infection. Functional assays indicated that Tim-3 mediates suppression of CD107a degranulation in NK cells and CD4+ T cells, while it fails to inhibit the production of IFN-γ by NK cells. Analyses of downstream pathways using an antibody to block Tim-3 function demonstrated that Tim-3 can inhibit ERK and NFκB p65 signaling; however, it failed to suppress the NFAT pathway. Further, we found that the NFAT activity in NK cells was much higher than that in CD4+ T cells, indicating that NFAT pathway is important for promotion of IFN-γ production by NK cells.CONCLUSIONS:
Thus, our data show that the expression of Tim-3 on NK cells is insufficient to inhibit IFN-γ production. Collectively, our findings demonstrate a potential mechanism of Tim-3 regulation of NK cells and a target for HIV infection immunotherapy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Células Matadoras Naturais
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Linfócitos T CD4-Positivos
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Infecções por HIV
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HIV-1
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Fatores de Transcrição NFATC
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Receptor Celular 2 do Vírus da Hepatite A
Limite:
Adult
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article