Blockade of IL-7Rα alleviates collagen-induced arthritis via inhibiting Th1 cell differentiation and CD4+ T cell migration

Cai, Li; Xu, Haiyan; Zhang, Han; Zhang, Lili; Wang, Guojue; Nie, Hong

doi:10.1016/j.molimm.2016.09.017

Cited by 9 publications

(6 citation statements)

References 37 publications

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“…The IL‐7/IL‐7R axis plays a controversial role in osteoclastogenic disease. Although there has been an indication that blockade of IL‐7R/IL‐7Rα could alleviate CIA recently [28,30], whether this blockade could prevent bone destruction in CIA mice and the mechanism by which this occurs are still unclear. This study provides the evidence that IL‐7/IL‐7R pathway plays a dual effect on osteoclastogenesis and that this axis may be a potential therapeutic target for RA.…”

Section: Discussionmentioning

confidence: 99%

“…One group was administrated with anti‐IL‐7Rα (Purified NA/LE Rat Anti‐Mouse CD127, BD Bioscience, USA) and the other with an isotype control (Purified NA/LE Rat IgG2a κ isotype Control, BD Bioscience, USA) every 3 days. After day 21, the mice were observed daily in order to assess and grade the disease severity daily based on the standards described previously [28]. The total score for the paws was used as the clinical score.…”

Section: Methodsmentioning

confidence: 99%

“…There are two parts of RA pathogenesis including inflammation and joint damage. In addition to its suggested role in inflammatory process of RA via CD4 + T cells [28,29] and myeloid cells [30,31], whether and how IL‐7/IL‐7R pathway function in the context of osteoimmunology remain elusive.…”

Section: Introductionmentioning

confidence: 99%

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Dual effect of IL‐7/IL‐7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis

Cai

et al. 2021

Immunology

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The IL‐7/IL‐7R pathway plays a vital role in the immune system, especially in the inflammatory response. Monocytes/macrophages (osteoclast precursors) have been recently recognized as important participants in the osteoclastogenesis of rheumatoid arthritis (RA) patients. Here, we aimed to investigate the therapeutic potential of IL‐7/IL‐7R pathway in RA and to determine whether it could restrain osteoclastogenic functions and therefore ameliorate RA. Firstly, collagen‐induced arthritis (CIA) mice were administered with IL‐7Rα‐target antibodies to assess their therapeutic effect on arthritis. We found that blockade of the IL‐7/IL‐7R pathway protected CIA mice from bone destruction in addition to inducing inflammatory remission, by altering the RANKL/RANK/OPG ratio and consequently decreasing osteoclast formation. To explore the effect and mechanism of this pathway, bone marrow cells were induced to osteoclasts and treated with IL‐7, a STAT5 inhibitor or supernatants from T cells. The results showed that the IL‐7/IL‐7R pathway played a direct inhibitory role in osteoclast differentiation via STAT5 signalling pathway in a RANKL‐induced manner. We applied flow cytometry to analyse the effect of IL‐7 on T‐cell RANKL expression and found that IL‐7/IL‐7R pathway had an indirect role in the osteoclast differentiation process by enhancing the RANKL expression on T cells. In conclusion, the IL‐7/IL‐7R pathway exhibited a dual effect on osteoclastogenesis of CIA mice by interacting with osteoimmunology processes and could be a novel therapeutic target for autoimmune diseases such as RA.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Dual effect of IL‐7/IL‐7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis

Cai

et al. 2021

Immunology

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“…Monoclonal antibodies (MAb) that antagonize the IL-7Rα (111) are in investigation for treatment of a range of autoimmune diseases and inflammatory conditions, including diabetes (112), multiple sclerosis, rheumatoid arthritis (113, 114), and inflammatory bowel disease (115). The aim of these approaches is to suppress aberrant memory CD4 + T cell responses (116). A single intravenous administration of anti-CD127 antagonist antibody resulted in inhibition of antigen-specific memory CD4 + T cell responses and decreased chronic inflammation in primates that was sustained for 11 weeks (111).…”

Section: Therapeutic Implications Of Art-mediated Restoration Of Cd4+mentioning

confidence: 99%

Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure

et al. 2019

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Recent studies demonstrate that the stable HIV-1 reservoir in resting CD4 + T cells is mostly formed from viruses circulating when combination antiretroviral therapy (ART) is initiated. Here we explore the immunological basis for these observations. Untreated HIV-1 infection is characterized by a progressive depletion of memory CD4 + T cells which mostly express CD127, the α chain of the IL-7 receptor (IL-7R). Depletion results from both direct infection and bystander loss of memory CD4 + T cells in part attributed to dysregulated IL-7/IL-7R signaling. While IL-7/IL7R signaling is not essential for the generation of effector CD4 + T cells from naïve cells, it is essential for the further transition of effectors to memory CD4 + T cells and their subsequent homeostatic maintenance. HIV-1 infection therefore limits the transition of CD4 + T cells from an effector to long-lived memory state. With the onset of ART, virus load (VL) levels rapidly decrease and the frequency of CD127 + CD4 + memory T cells increases, indicating restoration of effector to memory transition in CD4 + T cells. Collectively these data suggest that following ART initiation, HIV-1 infected effector CD4 + T cells transition to long-lived, CD127 + CD4 + T cells forming the majority of the stable HIV-1 reservoir. We propose that combining ART initiation with inhibition of IL-7/IL-7R signaling to block CD4 + T cell memory formation will limit the generation of long-lived HIV-infected CD4 + T cells and reduce the overall size of the stable HIV-1 reservoir.

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“…In addition, IL-7 drives T-cell-dependent autoimmunity, induces inflammatory cytokines secreted by macrophages/monocytes and leads to tissue destruction [49]. IL-7 also increases responsiveness of CD4+T-cells and lowers the suppressive ability of regulatory T-cells [50], mediating RA pathogenesis by inducing production of potent proangiogenic factors from macrophages and endothelial cells [51].…”

Section: Chondrocytes Indirectly Involve In Ra Through Crosstalk Withmentioning

confidence: 99%

Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

Tseng

Chen

Chang

et al. 2020

IJMS

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Rheumatoid arthritis (RA) is one of the inflammatory joint diseases that display features of articular cartilage destruction. The underlying disturbance results from immune dysregulation that directly and indirectly influence chondrocyte physiology. In the last years, significant evidence inferred from studies in vitro and in the animal model offered a more holistic vision of chondrocytes in RA. Chondrocytes, despite being one of injured cells in RA, also undergo molecular alterations to actively participate in inflammation and matrix destruction in the human rheumatoid joint. This review covers current knowledge about the specific cellular and biochemical mechanisms that account for the chondrocyte signatures of RA and its potential applications for diagnosis and prognosis in RA.

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Blockade of IL-7Rα alleviates collagen-induced arthritis via inhibiting Th1 cell differentiation and CD4+ T cell migration

Cited by 9 publications

References 37 publications

Dual effect of IL‐7/IL‐7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis

Dual effect of IL‐7/IL‐7R signalling on the osteoimmunological system: a potential therapeutic target for rheumatoid arthritis

Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure

Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

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