Interleukin-17 induces pyroptosis in osteoblasts through the NLRP3 inflammasome pathway in vitro

Lei, Lihong; Sun, Jianwei; Han, Jiayin; Jiang, Xiaojian; Wang, Zhongxiu; Chen, Lili

doi:10.1016/j.intimp.2021.107781

Cited by 47 publications

(35 citation statements)

References 37 publications

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“…With respect to osteoblasts, TNF-α and IL-17A are able to inhibit osteoblastogenesis by inducing the upregulation of Dickkopf (Dkk)-1, which in turn inhibits the Wnt-β-catenin-signaling necessary for differentiation of stromal mesenchymal cells into osteoblasts [ 7 , 62 ]. IL-17A has the ability to downregulate osteoblast genes associated with bone formation, such as alkaline phosphatase (ALP), osteocalcin (OCN), and Runt-related transcription factor 2 (Runx-2), and even cause pyroptosis in already differentiated osteoblasts [ 63 , 64 ].…”

Section: Osteoimmunology and Th17/treg Imbalancementioning

confidence: 99%

Senescent CD4+CD28− T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

González-Osuna

Sierra-Cristancho

Cafferata

et al. 2022

IJMS

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Senescent cells express a senescence-associated secretory phenotype (SASP) with a pro-inflammatory bias, which contributes to the chronicity of inflammation. During chronic inflammatory diseases, infiltrating CD4+ T lymphocytes can undergo cellular senescence and arrest the surface expression of CD28, have a response biased towards T-helper type-17 (Th17) of immunity, and show a remarkable ability to induce osteoclastogenesis. As a cellular counterpart, T regulatory lymphocytes (Tregs) can also undergo cellular senescence, and CD28- Tregs are able to express an SASP secretome, thus severely altering their immunosuppressive capacities. During periodontitis, the persistent microbial challenge and chronic inflammation favor the induction of cellular senescence. Therefore, senescence of Th17 and Treg lymphocytes could contribute to Th17/Treg imbalance and favor the tooth-supporting alveolar bone loss characteristic of the disease. In the present review, we describe the concept of cellular senescence; particularly, the one produced during chronic inflammation and persistent microbial antigen challenge. In addition, we detail the different markers used to identify senescent cells, proposing those specific to senescent T lymphocytes that can be used for periodontal research purposes. Finally, we discuss the existing literature that allows us to suggest the potential pathogenic role of senescent CD4+CD28- T lymphocytes in periodontitis.

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Section: Osteoimmunology and Th17/treg Imbalancementioning

confidence: 99%

Senescent CD4+CD28− T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

González-Osuna

Sierra-Cristancho

Cafferata

et al. 2022

IJMS

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“…Considering that bulk RNA sequencing measures the mRNA expression of the entire tumor tissue, which includes tumor cells, stromal cells, immune cells, and some extracellular cytokines, we speculated that IL27 could promote programmed cell death of tumor cells by enhancing effector immune cells. In effect, NOD-like receptor signaling pathway has also been reported to correlate with pyroptosis ( 40 ). Consistent with our speculation that programmed cell death occurs in tumor cells, we have previously demonstrated that high IL27 expression indeed is associated with elevated immune response and improved survival in melanoma.…”

Section: Resultsmentioning

confidence: 99%

Integrative Characterization of the Role of IL27 In Melanoma Using Bioinformatics Analysis

et al. 2021

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BackgroundIL27 has been reported to play dual roles in cancer; however, its effects on the tumor microenvironment (TME), immunotherapy, and prognosis in melanoma remain largely unclear. This study was aimed to uncover the effects of IL27 on TME, immunotherapy and prognosis in patients with melanoma.MethodsRNA-seq data, drug sensitivity data, and clinical data were obtained from TCGA, GEO, CCLE, and CTRP. Log-rank test was used to determine the survival value of IL27. Univariate and multivariate Cox regression analyses were employed to determine the independent predictors of survival outcomes. DAVID and GSEA were used to perform gene set functional annotations. ssGSEA was used to explore the association between IL27 and immune infiltrates. ConsensusClusterPlus was used to classify melanoma tissues into hot tumors or cold tumors.ResultsClinically, IL27 was negatively correlated with Breslow depth (P = 0.00042) and positively associated with response to radiotherapy (P = 0.038). High IL27 expression showed an improved survival outcome (P = 0.00016), and could serve as an independent predictor of survival outcomes (hazard ratio: 0.32 - 0.88, P = 0.015). Functionally, elevated IL27 expression could induce an enhanced immune response and pyroptosis (R = 0.64, P = 1.2e-55), autophagy (R = 0.37, P = 7.1e-17) and apoptosis (R = 0.47, P = 1.1e-27) in patients with melanoma. Mechanistically, elevated IL27 expression was positively correlated with cytotoxic cytokines (including INFG and GZMB), enhanced immune infiltrates, and elevated CD8/Treg ratio (R = 0.14, P = 0.02), possibly driving CD8+ T cell infiltration by suppressing β-catenin signaling in the TME. Furthermore, IL27 was significantly associated with hot tumor state, multiple predictors of response to immunotherapy, and improved drug response in patients with melanoma.ConclusionsIL27 was correlated with enriched CD8+ T cells, desirable therapeutic response and improved prognosis. It thus can be utilized as a promising modulator in the development of cytokine-based immunotherapy for melanoma.

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“…As a result, disruption in either hematopoiesis or vascularization should undoubtedly impact osteoclastogenesis ( Buettmann et al, 2019 ). Although our mechanistic studies revolved around myeloid cells from which the osteoclasts arise, it is worth noting that the inflammasome-GSDM pathways are functional in the osteoblast lineage ( Zhang and Wei, 2021b ; Lei et al, 2021 ; Jiang et al, 2021 ). Therefore, osteoblast lineage autonomous actions of these pathways in bone healing cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

Sun

Chün²,

Xiao³

et al. 2022

eLife

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IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking either GSDM compared with wild-type (WT) mice, indicating that fracture healing was compromised in mutant mice. However, compound loss of GSDMD and GSDME did not exacerbate the outcomes, suggesting shared actions of both GSDMs in fracture healing. Mechanistically, bone injury induced IL-1β and IL-18 secretion in vivo, a response that was mimicked in vitro by bone debris and ATP, which function as inflammatory danger signals. Importantly, the secretion of these cytokines was attenuated in conditions of GSDMD deficiency. Finally, deletion of IL-1 receptor reproduced the phenotype of Gsdmd or Gsdme deficient mice, implying that inflammatory responses induced by the GSDM-IL-1 axis promote bone healing after fracture.

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Interleukin-17 induces pyroptosis in osteoblasts through the NLRP3 inflammasome pathway in vitro

Cited by 47 publications

References 37 publications

Senescent CD4+CD28− T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

Senescent CD4+CD28− T Lymphocytes as a Potential Driver of Th17/Treg Imbalance and Alveolar Bone Resorption during Periodontitis

Integrative Characterization of the Role of IL27 In Melanoma Using Bioinformatics Analysis

Fracture healing is delayed in the absence of gasdermin-interleukin-1 signaling

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