Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease

Nakamura, Akihiro; Zeng, Fanxing; Nakamura, Sayaka; Reid, Kyle T; Gracey, Eric; Lim, Melissa; Leng, Lin; Jo, Sungsin; Park, Ye‐Soo; Kusuda, Masaki; Machhar, Rohan; Foroozan-Boroojeni, Shaghayegh; Wu, Bangbiao; Rossomacha, Evgeny; Ciccia, Francesco; Rockel, Jason S.; Kapoor, Mohit; Inman, Robert D.; Jurišica, Igor; Crome, Sarah Q.; Bucala, Richard; Haroon, Nigil

doi:10.1126/scitranslmed.abg1210

Cited by 40 publications

(22 citation statements)

References 51 publications

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“…Macrophage migration inhibitory factor (MIF) is a multipotent cytokine involved in both inflammatory processes and anti-tumor immune response, having the properties of an enzyme, chemokine, and hormone simultaneously ( Sumaiya et al, 2021 ). As a proinflammatory mediator secreted by numerous immune cells, MIF promotes inflammation and autoimmune diseases mainly by binding with the receptor CD74 and co-receptor CD44, CXCR4, or CXCR2 ( Liehn et al, 2013 ; Nakamura et al, 2021 ; Wallace et al, 2021 ). Previous studies have shown that the carcinogenic role MIF plays is related to the activation of p53, Ras/MAPK, and Akt pathways in the inflammation–cancer axis ( Mittelbronn et al, 2011 ; Wang et al, 2017 ; Liu et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of novel tumor microenvironment-associated genes in gastric cancer based on single-cell RNA-sequencing datasets

et al. 2022

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Tumor microenvironment and heterogeneity play vital roles in the development and progression of gastric cancer (GC). In the past decade, a considerable amount of single-cell RNA-sequencing (scRNA-seq) studies have been published in the fields of oncology and immunology, which improve our knowledge of the GC immune microenvironment. However, much uncertainty still exists about the relationship between the macroscopic and microscopic data in transcriptomics. In the current study, we made full use of scRNA-seq data from the Gene Expression Omnibus database (GSE134520) to identify 25 cell subsets, including 11 microenvironment-related cell types. The MIF signaling pathway network was obtained upon analysis of receptor–ligand pairs and cell–cell interactions. By comparing the gene expression in a wide variety of cells between intestinal metaplasia and early gastric cancer, we identified 64 differentially expressed genes annotated as immune response and cellular communication. Subsequently, we screened these genes for prognostic clinical value based on the patients’ follow-up data from The Cancer Genome Atlas. TMPRSS15, VIM, APOA1, and RNASE1 were then selected for the construction of LASSO risk scores, and a nomogram model incorporating another five clinical risk factors was successfully created. The effectiveness of least absolute shrinkage and selection operator risk scores was validated using gene set enrichment analysis and levels of immune cell infiltration. These findings will drive the development of prognostic evaluations affected by the immune tumor microenvironment in GC.

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Section: Discussionmentioning

confidence: 99%

Identification of novel tumor microenvironment-associated genes in gastric cancer based on single-cell RNA-sequencing datasets

et al. 2022

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“…In affected patients subclinical gut inflammation, initiated by intestinal dysbiosis, is essential to the prospective development of inflammation in the synovial-entheseal complex. Although the crucial role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including JSpA, is well-known, the role of MIF is generally ignored, but recently validated (7,8) Along the same lines, Romero-López et al discuss the clinical and translational features of inflammatory foot involvement in SpA. The authors highlight the predominance of tarsal affection in JSpA patients among several cohorts.…”

Section: Overview Of the Issuementioning

confidence: 99%

“…In affected patients subclinical gut inflammation, initiated by intestinal dysbiosis, is essential to the prospective development of inflammation in the synovial–entheseal complex. Although the crucial role of IL17/23 axis, TNF-α, and IL-7 in the pathophysiology of SpA, including JSpA, is well-known, the role of MIF is generally ignored, but recently validated ( 7 , 8 ). The strong correlation of osteitis with low-grade IBD, established in children with ErA by elevated concentration of fecal calprotectin (fCAL) ( Lamot et al ), emerges as the central event in the early stages of SpA.…”

Section: Overview Of the Issuementioning

confidence: 99%

Editorial: Juvenile Spondyloarthritis: From Basic Science to Clinical Translation

2022

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“…MIF is produced by a wide variety of innate and adaptive immune and non-immune cells [110]. MIF is implicated in several biological functions and may also modulate bone metabolism by promoting both osteoclastic and osteoblastic activity [111][112][113][114][115]. Binding of MIF to CD74 on B cells may induce survival, proliferation, and maturation via NF-κB mediated transcription [116][117][118].…”

Section: Antibodies Directed Against Intracellular Molecules Involved...mentioning

confidence: 99%

B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis

Wilbrink

Spoorenberg

Verstappen

et al. 2021

IJMS

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Extensive research into ankylosing spondylitis (AS) has suggested the major role of genetics, immune reactions, and the joint–gut axis in its etiology, although an ultimate consensus does not yet exist. The available evidence indicates that both autoinflammation and T-cell-mediated autoimmune processes are actively involved in the disease process of AS. So far, B cells have received relatively little attention in AS pathogenesis; this is largely due to a lack of conventional disease-defining autoantibodies. However, against prevailing dogma, there is a growing body of evidence suggestive of B cell involvement. This is illustrated by disturbances in circulating B cell populations and the formation of auto-reactive and non-autoreactive antibodies, along with B cell infiltrates within the axial skeleton of AS patients. Furthermore, the depletion of B cells, using rituximab, displayed beneficial results in a subgroup of patients with AS. This review provides an overview of our current knowledge of B cells in AS, and discusses their potential role in its pathogenesis. An overarching picture portrays increased B cell activation in AS, although it is unclear whether B cells directly affect pathogenesis, or are merely bystanders in the disease process.

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Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease

Abstract: Macrophage migration inhibitory factor produced by neutrophils worsens spondyloarthritis by inducing a pathogenic T H 17 phenotype in T regs .

Cited by 40 publications

References 51 publications

Identification of novel tumor microenvironment-associated genes in gastric cancer based on single-cell RNA-sequencing datasets

Identification of novel tumor microenvironment-associated genes in gastric cancer based on single-cell RNA-sequencing datasets

Editorial: Juvenile Spondyloarthritis: From Basic Science to Clinical Translation

B Cell Involvement in the Pathogenesis of Ankylosing Spondylitis

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