IL-23 specifically contributes to the inflammatory process of multiple chronic inflammatory autoimmune disorders, including psoriasis, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.
Asymptomatic humans with rheumatoid arthritis (RA)-specific autoantibodies showed identical changes in the activity and glycosylation of autoreactive IgG antibodies before shifting to the inflammatory phase of RA; thus, our results identify an IL-23-T<sub>H</sub>17 cell-dependent pathway that controls autoantibody activity and unmasks a preexisting breach in immunotolerance.
Besides Th17- and Treg-associated cytokines, elevated expression of IL-27/IL-23 cytokines might also be responsible for increased disease severity in female patients with RA.
Collectively, our data suggest that systemic IL-23 exposure induces the expansion of a myeloid lineage osteoclast precursor, and targeting IL-23 pathway may combat inflammation-driven bone destruction as observed in rheumatoid arthritis and other autoimmune arthritides.
Cytokines of the Interleukin (IL)-12 family, consisting of IL-12, IL-23, IL-27 and IL-35, are important regulators in (chronic) inflammatory disorders such as rheumatoid arthritis and multiple sclerosis, but also in cardiovascular diseases.
Following an analysis of the types of cells and antibodies found in joints affected by rheumatoid arthritis, it is concluded that both expression of oncogenes and the presence of retroviral sequences detectable by monoclonal antibodies to HTLV I p19 and p24 sequences are associated with early abnormal proliferation of apparently transformed cells at the site of initial cartilage and/or bone destruction.
In conclusion, our study demonstrates a functional effect of <i>IL12B</i> polymorphisms on IL-12p40 and IL-23 cytokine levels in RA patients and suggests a leading role for <i>IL12B</i> rs17860508 in the genetic predisposition to RA, while <i>IL12B</i> rs3212227 significantly modify the RA risk in Bulgarian population.
In early RA, the involvement of anticitrullinated protein antibodies in RA induction has been identified with a critical role of the IL-23/Th17 axis in the control of their pathogenicity.
In models of human immune cells in culture, CR6086 reduced key cytokine players of RA (IL-6 and VEGF expression in macrophages, IL-23 release from dendritic cells, IL-17 release from Th17 cells).
Interleukin-17 increased the expression of TLR2, TLR3 and TLR4 in RA FLS; IL-23 augmented the IL-17-induced expression of TLR2, TLR3 and TLR4 in RA FLS.
Low levels of wild-type (wt)COUP-TFI transgene expression did not inhibit neural cell fate and primarily enhanced neuron outgrowth from RA-treated P19 aggregates.
Signal transducer and activator of transcription 4 (STAT4) transmits signals induced by the cytokines interleukin (IL)-12, IL-23, and interferon (IFN)-γ, which play an important role in the development of rheumatoid arthritis (RA).
Since the IL-23/IL-17 pathway is known to associate with other autoimmune diseases, including rheumatoid arthritis (RA) and systemic sclerosis (SSc), we hypothesised that IL-23R could be a shared susceptibility gene.
Taken together, our findings demonstrate that IL-17 regulates SHP-2 expression and IL-17RA/STAT-3 dependent production of Cyr61, IL-23, GM-CSF and RANKL in AA-FLS and may reveal a new insight into the pathogenesis of RA.
The p19 subunit was abundantly expressed in RA but not in OA synovial tissues. p19 was most prominently expressed by RASF in the synovial lining layer and at the site of invasion, but no heterodimeric IL23 was detected at these sites.
The effect of proinflammatory cytokines [tumor necrosis factor α (TNFα) and IL-17] and Toll-like receptor (TLR) ligands [poly(I:C) and lipopolysaccharide (LPS)] on IL-17R expression and IL-12 and IL-23 production was studied in osteoarthritis (OA)- and rheumatoid arthritis (RA)-FLS, involved in Th1/Th17 differentiation.The effect of VIP was also determined.