Journal: Immunity & Ageing : I & A

Article Title: IL-35 promotes synovial fibroblast senescence via activation of cGAS-STING-TBK1-IRF3 pathway in rheumatoid arthritis

doi: 10.1186/s12979-026-00575-7

Figure Lengend Snippet: Expression patterns of IL-35 and its receptors in RA patients. A Schematic diagram of the IL-35 signaling pathway, illustrating its receptor complex (EBI3/p35/IL-12RB2/GP130) and downstream STAT1/STAT4 signaling cascades. B Box plot analysis of gene expression levels (EBI3, IL-12, IL-12RB2, and IL-6ST) in synovial tissues from RA patients and healthy controls. C Flow cytometry analysis of immune cell subsets in the peripheral blood of RA patients, including single cells, lymphocytes, viable cells (FVS780⁻), CD4⁺ T helper cells, CD45RO⁺ memory T helper cells, and IL-35-producing regulatory T cells (Tr35). D The ratio of Tr35 to CD45RO⁺ cells in peripheral blood was also assessed. E - G ELISA quantification of serum cytokine levels in RA patients and healthy controls. (***P<0.001)

Article Snippet: The primary antibodies against Bio GP130 (ABclonal, A3365, 1:1000, China), p53 (Proteintech, 10442-1-AP, 1:5000, China), p21 (Proteintech, 10355-1-AP, 1:2000), p16 (Proteintech, 10883-1-AP, 1:2000), p-STING (ABclonal, AP1369, 1:1000), STING (ABclonal, A21051, 1:5000), p-TBK1 (ABclonal, AP1026, 1:1000), TBK1 (ABclonal, A3458, 1:2000), p-IRF3 (Abcam, ab320082, 1:1000, China), IRF3 (Abcam, ab68481, 1:1000), STAT1 (Abcam, ab92506, 1:2000), p-STAT1 (Abcam, ab109461, 1:2000), STAT4 (Proteintech, 67568-2-Ig, 1:5000), p-STAT4(Abcam, ab28815, 1:1000), and GAPDH (Beyotime, AF5009, 1:2000) were used.

Techniques: Expressing, Gene Expression, Flow Cytometry, Enzyme-linked Immunosorbent Assay

Journal: Immunity & Ageing : I & A

Article Title: IL-35 promotes synovial fibroblast senescence via activation of cGAS-STING-TBK1-IRF3 pathway in rheumatoid arthritis

doi: 10.1186/s12979-026-00575-7

Figure Lengend Snippet: IL-35 signals primarily through the GP130 receptor to trigger cytosolic nucleic acid sensing, leading to STING-dependent cellular senescence, which could be inhibited by the STING antagonist C-176. A - E Functional analysis of IL-35 receptor requirement. Synovial fibroblasts were transfected with siRNA against IL12RB2 or GP130 before treatment with TNF-α and IL-35. (A) Proliferation was assessed by CCK-8 assay after 48 h. B , C Cytosolic dsDNA ( B ) and cGAMP ( C ) levels were quantified. D Senescence was evaluated by SA-β-gal staining. E Expression of senescence markers (p16, p21, p53) and STING pathway activation (p-STING/STING, p-TBK1/TBK1, p-IRF3/IRF3) was analyzed by western blot. F - J Validation of the STING pathway as a critical downstream effector. TNF-α-primed SFs were co-treated with IL-35 and the STING inhibitor C-176. F Proliferation (CCK-8 assay). G , H Cytosolic dsDNA ( G ) and cGAMP (H) levels. I Senescence (SA-β-gal staining). J Western blot analysis of senescence and STING pathway proteins. Data are presented as mean ± SD ( n = 3). * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001

Article Snippet: The primary antibodies against Bio GP130 (ABclonal, A3365, 1:1000, China), p53 (Proteintech, 10442-1-AP, 1:5000, China), p21 (Proteintech, 10355-1-AP, 1:2000), p16 (Proteintech, 10883-1-AP, 1:2000), p-STING (ABclonal, AP1369, 1:1000), STING (ABclonal, A21051, 1:5000), p-TBK1 (ABclonal, AP1026, 1:1000), TBK1 (ABclonal, A3458, 1:2000), p-IRF3 (Abcam, ab320082, 1:1000, China), IRF3 (Abcam, ab68481, 1:1000), STAT1 (Abcam, ab92506, 1:2000), p-STAT1 (Abcam, ab109461, 1:2000), STAT4 (Proteintech, 67568-2-Ig, 1:5000), p-STAT4(Abcam, ab28815, 1:1000), and GAPDH (Beyotime, AF5009, 1:2000) were used.

Techniques: Functional Assay, Transfection, CCK-8 Assay, Staining, Expressing, Activation Assay, Western Blot, Biomarker Discovery

Journal: Advances in Radiation Oncology

Article Title: Kupffer Cell-Derived Interleukin-6 Aggravates Radiation-Induced Liver Disease by Activating Hepatocyte STAT3 to Promote Ccng1 Transcription

doi: 10.1016/j.adro.2026.102003

Figure Lengend Snippet: Schematic of the Kuppfer cell (KC)-hepatocyte crosstalk mechanism in RILD. Irradiation (IR) stimulates KCs to secrete IL-6, which binds to the IL-6R/gp130 complex on hepatocytes to activate JAK; phosphorylated JAK induces STAT3 phosphorylation, and nuclear-translocated p-STAT3 binds to the Ccng1 promoter to promote its transcription; CCNG1 then regulates MDM2 to mediate ubiquitination-dependent TP53 proteolysis, ultimately enhancing hepatocyte apoptosis and driving radiation-induced liver disease (RILD) progression.

Article Snippet: Either a rat interleukin (IL)-6 antibody (anti-IL-6; R&D Systems, #AF506) or soluble rat gp130 Fc chimera protein (sgp130Fc; R&D Systems, #5029-RG-100) was intraperitoneally injected twice weekly at concentrations of 16.7 μg/kg and 0.5 mg/kg, respectively.

Techniques: Irradiation, Phospho-proteomics, Ubiquitin Proteomics