{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T02:12:59Z","timestamp":1755223979489,"version":"3.43.0"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T00:00:00Z","timestamp":1677974400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>PF\u201006651600 is a highly specific inhibitor of Janus\u2010activated kinase 3 and the Tec family of kinases. Regarding its dual function in the inhibition of both \u03b3c cytokine receptors and T cell receptor signaling, the present study aimed at evaluating the impact of PF\u201006651600 on the status of T\u2010helper cells (Th) as the central game players in the pathogenesis of rheumatoid arthritis (RA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>TCD4<jats:sup>+<\/jats:sup> cells were isolated from 34 RA patients and 15 healthy control individuals and were evaluated after treatment with PF\u201006651600.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>RA patients had higher percentages of TCD4<jats:sup>+<\/jats:sup> cells, CD4<jats:sup>+<\/jats:sup> PD\u20101<jats:sup>+<\/jats:sup> cells, and CD4<jats:sup>+<\/jats:sup> PD\u20101<jats:sup>+<\/jats:sup> TIGIT<jats:sup>+<\/jats:sup> cells compared to a healthy control group and the TCD4<jats:sup>+<\/jats:sup> cells of these patients showed higher interferon (IFN)\u2010\u03b3, tumor necrosis factor (TNF)\u2010\u03b1, and interleukin (IL)\u201017 secretion along with higher messenger RNA (mRNA) expressions of T\u2010bet. The percentage of CD4<jats:sup>+<\/jats:sup> PD\u20101<jats:sup>+<\/jats:sup> TIGIT<jats:sup>+<\/jats:sup> cells showed a reverse correlation with the Disease Activity Score of 28 joints of the RA patients. PF\u201006651600 caused a significant decrease in the mRNA expressions of T\u2010bet and RAR\u2010related orphan receptor \u03b3t and the secretion of interferon (IFN)\u2010\u03b3 and TNF\u2010\u03b1 in TCD4<jats:sup>+<\/jats:sup> cells of RA patients. On the other hand, the population of CD4<jats:sup>+<\/jats:sup> PD\u20101<jats:sup>+<\/jats:sup> TIGIT<jats:sup>+<\/jats:sup> cells was expanded under the influence of PF\u201006651600. This treatment also reduced the proliferation of TCD4<jats:sup>+<\/jats:sup> cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>PF\u201006651600 demonstrated a potential to modulate the activity of TCD4<jats:sup>+<\/jats:sup> cells in RA patients and to reduce the commitment of Th cells to the pathogenic Th1 and Th17 subsets. Further, it caused TCD4<jats:sup>+<\/jats:sup> cells to gain an exhausted phenotype which is associated with better prognosis in RA patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.14643","type":"journal-article","created":{"date-parts":[[2023,3,5]],"date-time":"2023-03-05T21:45:42Z","timestamp":1678052742000},"page":"740-750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy of PF\u201006651600 in alleviating the pro\u2010inflammatory capacity of <scp>CD4<\/scp><sup>+<\/sup> T cells in rheumatoid arthritis patients"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0753-1432","authenticated-orcid":false,"given":"Talar Ahmad Merza","family":"Mohammad","sequence":"first","affiliation":[{"name":"College of Pharmacy, Department of Pharmacology and Toxicology, Clinical Pharmacy Hawlar Medical University  Erbil 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