![\"JAK](\"https:\/\/onlinelibrary.wiley.com\/cms\/asset\/55413b94-2ff6-49c7-bd87-eb6503ebed96\/eji5943-gra-0001-m.png\")
<\/p>\n<\/p>\n
JAK inhibitors (baricitinib, tofacitinib, upadacitinib), except for filgotinib, significantly reduce plasmablast differentiation but only partly inhibit activation of na\u00efve B cells and exert a more modest effect on TNF and IL-8 production. Unlike other JAK inhibitors, filgotinib selectively inhibits STAT5 phosphorylation without affecting STAT3 phosphorylation in response to IL-21.<\/p>\n
<\/p>\n
B cells play a crucial role in autoimmune diseases, as evidenced by autoantibody responses and the effectiveness of B cell-targeted therapies. Janus kinase inhibitors (JAKi), which target downstream signaling of cytokine receptors, are potent rheumatic disease-modifying drugs. However, besides reducing inflammation, JAKi may impact the adaptive immune system. In this study, we examined the effects of JAKi on B-cell function using in vitro cultures and multiparameter flow cytometry. The results show a JAKi-mediated reduction in plasma cell differentiation, primarily by inhibition of memory B-cell stimulation and proliferation. JAKi exposure resulted in stalling R848, IL-2, and IL-21 stimulated B cells in an intermediate activated state with elevated na\u00efve cells displaying increased expression of CXCR5, CD71, CD22, and CD20. In addition, the data demonstrate a moderate JAKi-mediated reduction of B cell TNF and IL-8 cytokine expression following stimulation. Importantly, the efficacy varied greatly between drugs; tofacitinib and upadacitinib (pan JAKi; JAK1i) exhibited the strongest impact, while baricitinib (JAK1\/JAK2i) showed donor-dependent variation, and filgotinib (JAK1i) had no effect. All JAKi, except filgotinib, inhibited IL-2 or IL-21-induced STAT3 phosphorylation. Still, filgotinib demonstrated similar inhibition of phospho-STAT5 as other JAKi following IL-21. These findings underscore the therapeutic impact of JAKi through the modulation of B-cell functions.<\/p>","protected":false},"excerpt":{"rendered":"
JAK inhibitors (baricitinib, tofacitinib, upadacitinib), except for filgotinib, significantly reduce plasmablast differentiation but only partly inhibit activation of na\u00efve B cells and exert a more modest effect on TNF and IL-8 production. Unlike other JAK inhibitors, filgotinib selectively inhibits STAT5 phosphorylation without affecting STAT3 phosphorylation in response to IL-21. ABSTRACT B cells play a crucial … Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[112,42],"tags":[],"class_list":["post-27690","post","type-post","status-publish","format-standard","hentry","category-european-journal-of-immunology","category-publicaciones"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/27690","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=27690"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/27690\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=27690"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=27690"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=27690"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}