The role of IFI35 in lupus nephritis and related mechanisms

Zhang, Lihua; Zhu, Honglin; Li, Yisha; Dai, Xiaodan; Zhou, Bin; Li, Quan-Zhen; Zuo, Xiaoxia; Luo, Hui

doi:10.1080/14397595.2016.1270387

Cited by 19 publications

(13 citation statements)

References 34 publications

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“…For example, IFI35 is deemed a biomarker of neuroinflammation and therapeutic reaction in MS [ 71 ]. Additionally, IFI35 promotes the proliferation of mesangial cells, which is modulated by methyl CpG-binding domains in lupus nephritis [ 72 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis

Chen

Zhan

et al. 2022

Aging

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Objective: Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified. Methods: Gene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein–protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280. Results: Five datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: TRIM22 , IFI6 , IFITM1 , IFI35 , and IRF9 . Conclusions: Our bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.

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Section: Discussionmentioning

confidence: 99%

Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis

Chen

Zhan

et al. 2022

Aging

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“…As previously described (24), total RNA was isolated from mouse skin or lung tissue using Trizol (Invitrogen Life Technologies) according to the manufacturer's instructions. cDNA was prepared using the Reverse Transcription System (Promega).…”

Section: Methodsmentioning

confidence: 99%

The Fibrosis and Immunological Features of Hypochlorous Acid Induced Mouse Model of Systemic Sclerosis

et al. 2019

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Fibrotic animal models are critical for the pathogenesis investigations and drug explorations in systemic sclerosis (SSc). The bleomycin (BLM)-induced mouse model is the classical and most widely used fibrosis model. However, traditional subcutaneous injection of BLM rarely induced diffuse skin and lung lesions. Hypochlorous acid (HOCl)-induced mice are a more representative model that have diffuse cutaneous lesions, lung fibrosis and renal involvement. However, the fibrotic and immunological features of this model are not fully elucidated. Here, we injected BALB/c mice subcutaneously with HOCl used at different concentrations of HOCl (1:55, 1:70, and 1:110 NaClO: KH2PO4, hereafter named HOCl55, HOCl70, and HOCl110, respectively) for 6 weeks to induce fibrosis, and also used HOCl110 at different time course (4, 5, and 6 weeks). Morphological changes were observed via HE and Masson's trichrome staining. Immunohistochemistry or real-time PCR was used to detect inflammatory infiltrates, important fibrosis pathways and pro-inflammatory mediator expression. Flow cytometry was used to detect the alteration of immune cells in mouse spleen. Skin and lung fibrosis were most obvious in the HOCl55 group compared to lower concentration groups. In the HOCl110 group, dominant inflammatory infiltrates were found after 5 weeks, and significant fibrosis was found after 6 weeks. Then we explored the fibrosis and immunological profiles in the HOCl110 (6 weeks) group. Important fibrosis pathway proteins such as TGF-β, NF-κB, Smad3, p-Smad3, STAT3, and p-STAT3 were significantly elevated at week 6 in the HOCl110 group. Increased infiltration of CD4+T cells, CD8+T cells, CD20+B cells, and myofibroblasts was found both in skin and lung tissues. However, decreased CD4+T cells, CD8+T cells, monocytes and macrophages and increased CD19+B cells were found in the spleen tissues. The mRNA expression of fibrosis mediators such as IL-1β, IL-6, IL-17, IL-33, TNF-α, and CTGF was also upregulated in skin and lung tissues. In conclusion, HOCl induced fibrosis mouse model displayed systemic immune cell infiltration, pro-inflammatory mediator release, vasculopathy and fibrosis, which better mimicked human SSc than BLM-induced mice.

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“…to promote and amplify host inflammatory responses in sepsis (22). A number of recent reports showed that IFP35 family proteins are also involved in multiple inflammatory diseases, including hepatitis B virus-related acute-on-chronic liver failure (23), chronic obstructive pulmonary disease (24), and lupus nephritis (25). One recent clinical study demonstrated that the expression levels of IFP35 are correlated with the progression and clinical outcome of neuroinflammation in MS patients (26).…”

Section: Significancementioning

confidence: 99%

IFP35 family proteins promote neuroinflammation and multiple sclerosis

Jing

Yao

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

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Excessive activation of T cells and microglia represents a hallmark of the pathogenesis of human multiple sclerosis (MS). However, the regulatory molecules overactivating these immune cells remain to be identified. Previously, we reported that extracellular IFP35 family proteins, including IFP35 and NMI, activated macrophages as proinflammatory molecules in the periphery. Here, we investigated their functions in the process of neuroinflammation both in the central nervous system (CNS) and the periphery. Our analysis of clinical transcriptomic data showed that expression of IFP35 family proteins was up-regulated in patients with MS. Additional in vitro studies demonstrated that IFP35 and NMI were released by multiple cells. IFP35 and NMI subsequently triggered nuclear factor kappa B–dependent activation of microglia via the TLR4 pathway. Importantly, we showed that both IFP35 and NMI activated dendritic cells and promoted naïve T cell differentiation into Th1 and Th17 cells. Nmi−/−, Ifp35−/−, or administration of neutralizing antibodies against IFP35 alleviated the immune cells’ infiltration and demyelination in the CNS, thus reducing the severity of experimental autoimmune encephalomyelitis. Together, our findings reveal a hitherto unknown mechanism by which IFP35 family proteins facilitate overactivation of both T cells and microglia and propose avenues to study the pathogenesis of MS.

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The role of IFI35 in lupus nephritis and related mechanisms

Abstract: Our results demonstrated that IFI35 enhances the proliferation of mesangial cells and was regulated by MBD2 in LN.

Cited by 19 publications

References 34 publications

Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis

Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis

The Fibrosis and Immunological Features of Hypochlorous Acid Induced Mouse Model of Systemic Sclerosis

IFP35 family proteins promote neuroinflammation and multiple sclerosis

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