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.
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.
These lymphoid structures are associated with activation of the IL-23/Th17 pathway in RA and seemly in PsA, which could be useful to stratify RA patients.
The present review discusses the different aspects of IL-23 including its structural features, signal transduction pathway, preclinical, and clinical role in RA.
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.
We also highlight the key transcriptional factors required for Th17 development and therapeutic strategies to disrupt the interaction between IL-23 and IL-17 to prevent the end-organ damage in RA.
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).
The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy.
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.
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.
Using a microarray assay, our group newly identified interleukin (IL)‑12B, which encodes the p40 subunit common to IL‑12 and IL‑23, as one of the genes for which expression in fibroblast‑like synoviocytes from patients with rheumatoid arthritis (RA‑FLS) is induced by DcR3.
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.
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).
IL-23 specifically contributes to the inflammatory process of multiple chronic inflammatory autoimmune disorders, including psoriasis, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis.
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.
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.
These results indicate that SAA is a significant inducer of IL-23 and IL-1β in RA synoviocytes and potentially activates the IL-23/IL-17 pathway in the RA synovium.