Anti−IL-12/23 p40 antibody attenuates chronic graft-versus-host disease with lupus nephritis via inhibiting Tfh cell in mice

Gao, Yue; Zeng, Yu; Xue, Wenyao; Chen, Yucong; Li, Qianwen; Bian, Zhengying; Tang, Lei; Tang, Tiejun; Chen, Cong; Gao, Xiangdong; Guo, Wei

doi:10.1016/j.biopha.2020.110396

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…Thus, this antibody attenuates chronic graft-versus-host disease in murine models of lupus nephritis. 342 P40 mAb has been tested in many diseases in preclinical studies, such as psoriasis and Crohn's disease. 343,344 The results of phase 3 clinical trial including 312 adults with active psoriatic arthritis (PsA) show that ustekinumab (45/90 mg q12 weeks) led to significant and long-term improvement of symptoms/signs, including in patients who had previously received anti-TNF treatment.…”

Section: Manipulation Of Activatorsmentioning

confidence: 99%

The JAK/STAT signaling pathway: from bench to clinic

et al. 2021

Sig Transduct Target Ther

1,171

623

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The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pathway. Moreover, we highlight the role of the JAK/STAT pathway and its inhibitors in various diseases.

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Section: Manipulation Of Activatorsmentioning

confidence: 99%

The JAK/STAT signaling pathway: from bench to clinic

et al. 2021

Sig Transduct Target Ther

1,171

623

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“…SLE patients’ CD4 + T cells under Tfh-polarizing conditions treated with the anti-IL-12 antibody inhibited differentiation of CD4 + CXCR5 + PD-1 + T cells and CD4 + CXCR5 + PD-1 + Bcl-6 + T cells and downregulated IL-21 production ( 54 ). TCR-stimulated naive and memory CD4 + T cells from MRL/lpr mice showed comparable expression of mitochondrial reactive oxygen species (mROS) ( 55 ).…”

Section: Th1-related Inflammatory Cytokinesmentioning

confidence: 99%

“…On the contrary, MRL/lpr mice injected with the anti-IL-12 antibody inhibited lupus development, including less mesangial matrix deposition in glomeruli and reduced serum levels of anti-dsDNA, creatinine, and proteinuria ( 51 ). In cGVHD mice, injection of the anti-IL-12 antibody also inhibited mesangial cell proliferation and spleen enlargement, downregulated neutrophils in the mesangial area, reduced the renal histopathology score, reduced the serum levels of anti-dsDNA, reduced the number of CD4 + IFNγ + Th1 cells, CD4 + IL-17A + Th17 cells, and CD4 + CXCR5 + Tfh cells, and reduced the expression of transcription factors T-bet, Rorγt, Bcl-6, and PU.1, and inflammatory cytokines IFNγ, IL-9, IL-17A, TGF-β1, and IL-21 in spleen ( 54 ). Furthermore, a randomized-controlled study discussed the role of ustekinumab (an IL-12 inhibitor) in treatment of active SLE patients, showing that 62% patients who received ustekinumab at week 24 achieved a SLEDAI-2K responder index-4 (SRI-4) response than 33% patients who received placebo ( 56 ).…”

Section: Th1-related Inflammatory Cytokinesmentioning

confidence: 99%

Th1-related transcription factors and cytokines in systemic lupus erythematosus

Tang,

Wang,

Chen

et al. 2023

Front. Immunol.

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Systemic lupus erythematosus (SLE) is an inflammatory disorder related to immunity dysfunction. The Th1 cell family including Th1 cells, transcription factor T-bet, and related cytokines IFNγ, TNFα, IL-2, IL-18, TGF-β, and IL-12 have been widely discussed in autoimmunity, such as SLE. In this review, we will comprehensively discuss the expression profile of the Th1 cell family in both SLE patients and animal models and clarify how the family members are involved in lupus development. Interestingly, T-bet-related age-associated B cells (ABCs) and low-dose IL-2 treatment in lupus were emergently discussed as well. Collection of the evidence will better understand the roles of the Th1 cell family in lupus pathogenesis, especially targeting IL-2 in lupus.

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“…It is a complex immunological disorder of nephritis. 8 Lupus nephritis can cause weakened immunity, lymph node hyperplasia, and glomerulonephritis. Glomerulosclerosis or diffuse hyperplasia of kidney tissue can seriously impair metabolism and detoxification, and eventually lead to chronic renal failure, which can be life-threatening in severe cases.…”

Section: Introductionmentioning

confidence: 99%

Effects of Lactobacillus plantarum HFY15 on Lupus Nephritis in Mice by Regulation of the TGF-β1 Signaling Pathway

Cheng¹,

Yao²,

Wang³

et al. 2022

DDDT

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Objective In this study, the Lactobacillus plantarum HFY15 (LP-HFY15) strain isolated from naturally fermented yak yogurt was investigated. An animal model of lupus nephritis was established by pristane to verify the interventional effect of LP-HFY15 on mouse lupus nephritis by regulating the transforming growth factor-β1 (TGF-β1) signaling pathway. Materials and Methods Indexes in mouse serum and tissues were detected by kits, pathological changes in mouse kidney were observed by hematoxylin-eosin (H&E) staining, and quantitative polymerase chain reaction (qPCR) was used to detect TGF-β 1-related expression in mouse kidney tissue, which further elucidated the mechanism of LP-HFY15. Results LP-HFY15 decreased the elevation of urinary protein and the levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor alpha (TNF-α), and interferon γ (IFN-γ) in serum and kidney tissue. LP-HFY15 also reduced serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), triglyceride (TG), and raised total protein (TP), and albumin (ALB) levels in mice with nephritis. In addition, LP-HFY15 inhibited the positive rate of double-stranded deoxyribonucleic acid (dsDNA) antibodies in mice with nephritis. The observation of H&E sections showed that LP-HFY15 alleviated the glomerulus morphological incompleteness and inflammatory infiltration caused by nephritis. Further results showed that LP-HFY15 downregulated the mRNA expression of TGF-β1, vascular endothelial growth factor (VEGF), and nuclear factor kappa-B (NF-κB) in the kidneys of lupus nephritis mice, and the expression of inhibitor of NF-κB (IκB-α), copper/zinc superoxide dismutase (Cu/Zn-SOD), and manganese superoxide dismutase (Mn-SOD) was also upregulated. Conclusion These results indicated that LP-HFY15 plays a significant role in experimental intervention for lupus nephritis. The effect of LP-HFY15 was positively correlated with its concentration, and the effect was similar to that of prednisone at 10 9 CFU/kg.

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Anti−IL-12/23 p40 antibody attenuates chronic graft-versus-host disease with lupus nephritis via inhibiting Tfh cell in mice

Cited by 9 publications

References 21 publications

The JAK/STAT signaling pathway: from bench to clinic

The JAK/STAT signaling pathway: from bench to clinic

Th1-related transcription factors and cytokines in systemic lupus erythematosus

Effects of Lactobacillus plantarum HFY15 on Lupus Nephritis in Mice by Regulation of the TGF-β1 Signaling Pathway

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