TNF-alpha affects signature cytokines of th1 and th17 t cell subsets through differential actions on TNFR1 and TNFR2
Author
dc.contributor.author
Pesce Reyes, Bárbara Paz
Author
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Ribeiro, Carolina Hager
Author
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Larrondo Lillo, Milton Leonel
Author
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Ramos, Verónica
Author
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Soto Sáez, Lilian Andrea
Author
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Catalán Martina, Diego Francisco
Author
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Aguillón Gutiérrez, Juan Carlos
Admission date
dc.date.accessioned
2023-06-22T20:16:48Z
Available date
dc.date.available
2023-06-22T20:16:48Z
Publication date
dc.date.issued
2022
Cita de ítem
dc.identifier.citation
Int. J. Mol. Sci. 2022, 23, 9306.
es_ES
Identifier
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/10.3390/ijms23169306
Identifier
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https://repositorio.uchile.cl/handle/2250/194408
Abstract
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Tumor necrosis factor (TNF)- is a pleiotropic cytokine implicated in the etiology of
several autoimmune diseases, including rheumatoid arthritis (RA). TNF- regulates diverse effector
functions through the activation of TNF- receptor (TNFR)1 and TNFR2. Although the detrimental
role of this cytokine has been addressed in distinct disease settings, the effects of TNF- on cytokine
production by isolated CD4+ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that
contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that
TNF- promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-
and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed
that TNFR2 mediates the decrease in IFN-
production, while signaling through both receptors
augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients
present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T
cell types is similar between patients and controls. Since TNF- receptors levels in RA patients are
not significantly changed by the therapeutic blockade of TNF- , we propose that targeting TNFR2
may represent an alternative strategy to normalize the levels of key cytokines that contribute to
RA pathogenesis.