GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T <subscript>h</subscript> 1/T <subscript>h</subscript> 17 and regulatory T cells.
In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jg. 33 (2019-07-01), Heft 7, S. 8375-8385
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Zugriff:
Rheumatoid arthritis (RA) is an autoimmune disease associated with synovial hyperplasia and bone and cartilage destruction. T cells, notably T helper (T h )-1 and T h 17 cells, play a critical role in the pathologic process of RA. However, it remains unclear how T h 1 and T h 17 cells are regulated during RA. In this study, we report that the small ubiquitin-like protein X-linked gene in the G6PD cluster at Xq28 (GdX) regulates the balance of T h 17 and regulatory T (T reg ) cells during collagen-induced arthritis (CIA). We discovered that the splenocytes of GdX-knockout (KO) mice were insensitive to T-cell stimulants. Correspondingly, GdX-KO mice showed alleviative T h 1-mediated delayed-type hypersensitivity and were resistant to CIA compared with wild-type mice. GdX-KO mice showed fewer swollen paws, lower serum proinflammatory cytokine and anti-collagen IgG levels, and decreased synovial hyperplasia. Mechanistically, we observed that deletion of GdX decreased the transcription of proinflammatory cytokines and impaired the T h 1 and T h 17 differentiation but increased the T reg cell proliferation. Consistently, deletion of GdX decreased the transcription level of T-cell-specific T-box transcription factor and RAR-related orphan receptor-γ transcription factor but increased that of forkhead box P3 after being challenged with type-II collagen. These findings suggested that GdX functions as an important regulator of T h 1 or T h 17 and T reg cell balance during the inflammatory responses. Therefore, GdX may be a potential target for the therapy of RA.-Fu, Y., Liu, S., Wang, Y., Ren, F., Fan, X., Liang, J., Liu, C., Li, J., Ju, Y., Chang, Z. GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T h 1/T h 17 and regulatory T cells.
Titel: |
GdX/UBL4A-knockout mice resist collagen-induced arthritis by balancing the population of T <subscript>h</subscript> 1/T <subscript>h</subscript> 17 and regulatory T cells.
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Autor/in / Beteiligte Person: | Fu, Y ; Liu, S ; Wang, Y ; Ren, F ; Fan, X ; Liang, J ; Liu, C ; Li, J ; Ju, Y ; Chang, Z |
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Zeitschrift: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Jg. 33 (2019-07-01), Heft 7, S. 8375-8385 |
Veröffentlichung: | 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley ; <i>Original Publication</i>: [Bethesda, Md.] : The Federation, [c1987-, 2019 |
Medientyp: | academicJournal |
ISSN: | 1530-6860 (electronic) |
DOI: | 10.1096/fj.201802217RR |
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