JAK inhibitors disrupt T cell-induced proinflammatory macrophage activation.
RMD Open
; 9(1)2023 01.
Article
em En
| MEDLINE
| ID: mdl-36599629
ABSTRACT
OBJECTIVES:
Macrophage subsets, activated by T cells, are increasingly recognised to play a central role in rheumatoid arthritis (RA) pathogenesis. Janus kinase (JAK) inhibitors have proven beneficial clinical effects in RA. In this study, we investigated the effect of JAK inhibitors on the generation of cytokine-activated T (Tck) cells and the production of cytokines and chemokines induced by Tck cell/macrophage interactions.METHODS:
CD14+ monocytes and CD4+ T cells were purified from peripheral blood mononuclear cells from buffy coats of healthy donors. As representative JAK inhibitors, tofacitinib or ruxolitinib were added during Tck cell differentiation. Previously validated protocols were used to generate macrophages and Tck cells from monocytes and CD4+ T cells, respectively. Cytokine and chemokine including TNF, IL-6, IL-15, IL-RA, IL-10, MIP1α, MIP1ß and IP10 were measured by ELISA.RESULTS:
JAK inhibitors prevented cytokine-induced maturation of Tck cells and decreased the production of proinflammatory cytokines TNF, IL-6, IL-15, IL-1RA and the chemokines IL-10, MIP1α, MIP1ß, IP10 by Tck cell-activated macrophages in vitro (p<0.05).CONCLUSIONS:
Our findings show that JAK inhibition disrupts T cell-induced macrophage activation and reduces downstream proinflammatory cytokine and chemokine responses, suggesting that suppressing the T cell-macrophage interaction contributes to the therapeutic effect of JAK inhibitors.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Artrite Reumatoide
/
Inibidores de Janus Quinases
Tipo de estudo:
Guideline
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article