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Objective: Previous research reports that cell division control protein 42 (CDC42) is dysregulated in rheumatoid arthritis (RA). This study aimed to further explore the linkage of CDC42 with T-helper (Th) 1 and Th17 cell differentiation, and its implication in RA management.

Methods: After enrolling 80 RA patients, their blood CDC42, Th1 and Th17 cells were detected by RT-qPCR and flow cytometry, respectively, IFN-γ and IL-17A were detected by ELISA. Based on the treatment response at week 12, the patients were classified as response patients and no response patients. In addition, blood CDC42 was also detected after enrolling 40 healthy controls. Subsequently, naïve CD4 + T cells from RA patients were transfected with control, CDC42 overexpression and knockdown lentivirus, followed by differentiation assay.

Results: CDC42 was reduced in RA patients versus healthy controls (P < 0.001). In RA patients, CDC42 was negatively correlated with IFN-γ (P = 0.023), Th17 cells (P = 0.011) and IL-17A (P = 0.003) but not Th1 cells (P = 0.200). CDC42 presented an increasing trend after treatment (P < 0.001); besides, CDC42 at week 8 (P = 0.027) and week 12 (P < 0.001) were increased in response patients versus no response patients. Subsequent experiment showed that in RA CD4 + T cells, CDC42 overexpression reduced IFN-γ and IL-17A (both P < 0.05), while CDC42 knockdown elevated IL-17A (P < 0.05) but not IFN-γ (P > 0.05). Moreover, CDC42 overexpression inhibited, while CDC42 knockdown increased Th17 cell percentage (P < 0.05) but not Th1 cell percentage (P > 0.05).

Conclusions: CDC42 negatively correlates with disease risk and its elevation predicts better treatment response; it also inhibits Th17 but not Th1 cell differentiation in RA.

Titel:	Cell division control protein 42 correlates with lower disease risk and its elevation predicts better treatment response, and inhibits T-helper 17 cell differentiation in rheumatoid arthritis.
Autor/in / Beteiligte Person:	Yang, Y ; Huang, L ; Wu, B
Link:	Full Text Finder (Volltext)
Zeitschrift:	Inflammopharmacology, Jg. 30 (2022-12-01), Heft 6, S. 2117-2125
Veröffentlichung:	Basel ; Boston : Birkhäuser ; <i>Original Publication</i>: Dordrecht, The Netherlands ; Norwell, MA, USA : Kluwer Academic Publishers, c1991-, 2022
Medientyp:	academicJournal
ISSN:	1568-5608 (electronic)
DOI:	10.1007/s10787-022-00979-z
Schlagwort:	Humans Cell Differentiation Cell Division Arthritis, Rheumatoid metabolism Interleukin-17 metabolism Th17 Cells metabolism cdc42 GTP-Binding Protein metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Inflammopharmacology] 2022 Dec; Vol. 30 (6), pp. 2117-2125. <i>Date of Electronic Publication: </i>2022 Jun 23. MeSH Terms: Arthritis, Rheumatoid* / metabolism ; Interleukin-17* / metabolism ; Th17 Cells* / metabolism ; cdc42 GTP-Binding Protein* / metabolism ; Humans ; Cell Differentiation ; Cell Division References: Abbasi M, Mousavi MJ, Jamalzehi S, Alimohammadi R, Bezvan MH, Mohammadi H, Aslani S (2019) Strategies toward rheumatoid arthritis therapy; the old and the new. J Cell Physiol 234:10018–10031. 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Cell division control protein 42 correlates with lower disease risk and its elevation predicts better treatment response, and inhibits T-helper 17 cell differentiation in rheumatoid arthritis.