COPA (coatomer subunit α) syndrome is a newly recognised cause of interstitial lung disease in children and adults, frequently associated with arthritis and renal dysfunction.
Two new monogenic syndromes of inflammatory arthritis were discovered using whole exome sequencing: the coatomer subunit alpha syndrome because of rare mutations in coatomer subunit alpha and haploinsufficiency of A20 resulting from rare mutations in TNFAIP3.
However, in the case of combination therapy of IL-17A Ab and rIL-2 we have observed a beneficial effect in ameliorating the disease outcome as the arthritic index was decreased maximally at 15DPI with a significant reduction of arthritis compared to individual treatment.
These suggest that further applications, which suppress inflammatory enhancers, especially IL-17A, should be considered as a target for arthritis research and therapy.
Furthermore, they downregulated RORγt and Foxp3 expression in the joints, and inhibited IL-17 and promoted TGF-β expression in the serum, thereby improving arthritis, delaying radiological progression, and inhibiting synovial hyperplasia in CIA rats.
Circulating IL-17 level is significantly elevated in inflammatory arthritis and is related to the disease activity of AS and RA, suggesting that it plays an important role in the pathogenesis and progression of inflammatory arthritis (especially in AS and RA).
The histopathological features, clinical score, paw swelling, as well as the production of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and IL-17A were measured to determine the amelioration of butyrate on arthritis.
Our findings indicate that combined neutralization of TNF-α and IL-17A was considerably more effective than monotherapy in improving collagen-induced arthritis disease even when administered at a minimally efficacious dose.
Moreover, treatment with IL-1 antagonists effectively lowered the proportions of NCR<sup>+</sup> ILC3s and IL-17A producing ILC3s in Ncf1<sup>-/-</sup> arthritic mice and ameliorated the joint inflammation.
These results suggest that TOV has significant anti-arthritic effects on collagen-induced arthritis in rats, which may be attributed to the inhibition of the levels of IL-1β, IL-6, IL-8, IL-17A, TNF-α, MMP-3 and MMP-9, and the increase of IL-10 in serum as well as down-regulation of the protein expression of COX-2 and iNOS in synovial tissues via suppressing the phosphorylation and degradation of IκB.
GPI-specific productions of IFNγ and IL-17 from T cells in lymph nodes were evaluated.<b>Results</b>: Cl-amidine treatment significantly reduced arthritis severity while ACPA titers tended to be lower, but not significantly different compared to the control.
Immunoprofiling of synovial fluid showed that the proportion of inflammatory IL-17-producing CD4<sup>+</sup> T cells and amount of IL-17 were notably increased in synovial fluid with every recurrent flair, and correlated with the increase in number of synovial neutrophils, suggesting a potential role of T helper 17 (Th17) cells in neutrophil-driven inflammation during pseudogout arthritis.
In addition, we have demonstrated that the administration of a neutralizing antibody against IL-17 attenuates joint symptoms, swelling and leukocytes infiltration to the inflamed tissue, possibly providing a new strategy for the treatment of gouty inflammation and/or arthritis.
CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015).
These findings suggest that the chronic production of a high level of LL-37 may synchronize with its downstream proinflammatory cytokines, especially IL17A, contributing to the co-operative enhancement of pathogenesis mechanisms of inflammatory arthritis, such as high production of proinflammatory cytokines and mediators together with the activation of HA-metabolism-associated genes and cell invasion.
The severity of arthritis was significantly reduced in Th17 cell-deficient mice, suggesting that Th17 cells have additional, IL-17A-independent roles in inflammatory arthritis.