FGF2 cooperates with IL-17 to promote autoimmune inflammation

Shao, Xiaofeng; Chen, Siyuan; Yang, Dae Suk; Cao, Meiqun; Yao, Yikun; Wu, Zhengxi; Li, Ningli; Shen, Nan; Li, Xiaoxia; Song, Xiaohe; Qian, Youcun

doi:10.1038/s41598-017-07597-8

Cited by 24 publications

(33 citation statements)

References 40 publications

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“…The extent of the additional effect of the anti-FGF2 antibody correlated with the extent of the tumour response to radiation alone. These data are consistent with previous reports showing inhibition or depletion of macrophages after irradiation leads to prolonged tumour growth delay or in some cases augments immune checkpoint therapy 35,38,60,61 .…”

Section: Discussionsupporting

confidence: 93%

“…In non-cancer models, effects on macrophages by FGF2 have not been directly described. However, enhanced leucocyte recruitment directed by FGF2 62 , and promotion of autoimmune arthritis 61 are both suggestive of potential macrophage involvement. FGF2 deficiency leads to enhanced colitis in murine models 63 , demonstrating the capacity of FGF2 to mediate inflammation.…”

Section: Discussionmentioning

confidence: 99%

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FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy

Buzzelli

Jones

et al. 2020

Nat Commun

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Regulation of the programming of tumour-associated macrophages (TAMs) controls tumour growth and anti-tumour immunity. We examined the role of FGF2 in that regulation. Tumours in mice genetically deficient in low-molecular weight FGF2 (FGF2 LMW) regress dependent on T cells. Yet, TAMS not T cells express FGF receptors. Bone marrow derived-macrophages from Fgf2 LMW−/− mice co-injected with cancer cells reduce tumour growth and express more inflammatory cytokines. FGF2 is induced in the tumour microenvironment following fractionated radiation in murine tumours consistent with clinical reports. Combination treatment of in vivo tumours with fractionated radiation and a blocking antibody to FGF2 prolongs tumour growth delay, increases long-term survival and leads to a higher iNOS + /CD206 + TAM ratio compared to irradiation alone. These studies show for the first time that FGF2 affects macrophage programming and is a critical regulator of immunity in the tumour microenvironment.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy

Buzzelli

Jones

et al. 2020

Nat Commun

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“…The results of the present study were in agreement with numerous previous studies. For example, Shao et al ( 46 ) demonstrated that ectopic expression of FGF2 in mouse joints enhanced the levels of IL-17-induced inflammatory cytokines and the production of chemokines in the tissue, which resulted in exacerbated symptoms of autoimmune arthritis. Drosos et al ( 47 ) revealed that the upregulation of hypoxia-inducible factor-1α and FOSL2 in perivascular adipose tissues may enhance leptin gene transcription, which further induces vascularization and inflammation, ultimately contributing to increased atherosclerotic plaque burden in the coronary arteries.…”

Section: Discussionmentioning

confidence: 99%

Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

Yang

Wei

et al. 2018

Mol Med Report

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Exosomal micro (mi)RNAs have been suggested to have important roles in abdominal obesity, and to be associated with metabolic alterations via posttranscriptional regulation of target genes. However, exosomal miRNA profiles in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have rarely been investigated. In the present study, microarray data were obtained from the Gene Expression Omnibus database with the following accession numbers: GSE68885 (exosomal miRNAs in SAT obtained from seven patients with obesity and five lean patients), GSE50574 (exosomal miRNAs in VAT obtained from seven patients with obesity and five lean patients) and GSE29718 [mRNAs in SAT (obtained from seven patients with obesity and eight lean patients) and VAT (obtained from three patients with obesity and two lean patients)]. Differentially expressed (DE)-miRNAs and differentially expressed genes (DEGs) were identified using the Linear Models for Microarray Data method, and mRNA targets of DE-miRNAs were predicted using the miRWalk2.0 database. Potential functions of DE-miRNA target genes were determined using the Database for Annotation, Visualization and Integrated Discovery. As a result, 10 exosomal DE-miRNAs were identified in SAT between patients with obesity and lean patients, while 58 DE-miRNAs were identified in VAT between patients with obesity and lean patients. miRNA (miR)-4517 was revealed to be a downregulated exosomal miRNA between SAT and VAT, while the other DE-miRNAs were SAT-(e.g. hsa-miR-3156-5p and hsa-miR-4460) or VAT-(e.g. hsa-miR-582-5p, hsa-miR-566 and miR-548) specific. Following overlapping with the target genes of DE-miRNAs, only one DEG [cluster of differentiation 86 (CD86)] was identified in SAT samples, whereas 25 DEGs (e.g. fibroblast growth factor 2 (FGF2), FOS like 2, AP-1 transcription factor subunit (FOSL2); and adenosine monophosphate deaminase 3 (AMPD3)] were identified in VAT samples. CD86 was revealed to be regulated by hsa-miR-3156-5p; whereas FGF2, FOSL2 and AMPD3 were revealed to be regulated by hsa-miR-582-5p, hsa-miR-566 and miR-548, respectively. Functional enrichment analysis demonstrated that these target genes may be associated with inflammation. In conclusion, exosomal miRNAs may represent underlying therapeutic targets for the treatment of abdominal obesity and metabolic disorders via regulation of inflammatory genes.

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“…Monney et al showed that Tim-3 acts as an immunosuppressive factor in Th1 cells [ 21 ]. IL-17 has been reported to be involved in the development of inflammation and plays an important role in autoimmune diseases [ 22 , 23 ]. In the present study, we identified increased serum Tim-3 and IL-17 levels in SLE patients.…”

Section: Discussionmentioning

confidence: 99%

Association of Serum T cell Immunoglobulin Domain and Mucin-3 and Interleukin-17 with Systemic Lupus Erythematosus

Jin

Bai

Zhou

et al. 2018

Med Sci Monit Basic Res

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BackgroundPrevious studies have shown that T cell immunoglobulin domain and mucin-3 (Tim-3) and interleukin-17 (IL-17) are implicated in the development of several autoimmune diseases. However, it is unclear whether these proteins contribute to the pathogenesis of systemic lupus erythematosus (SLE). The purpose of this study was to evaluate SLE patient serum Tim-3 and IL-17 levels, and to assess correlations between these proteins and major clinical parameters of SLE.Material/MethodsOverall, 55 SLE patients and 55 healthy controls were recruited in a case-control study. Serum Tim-3 and IL-17 levels were quantified using an enzyme-linked immunosorbent assay (ELISA) kit.ResultsSerum Tim-3 and IL-17 levels in SLE patients were significantly elevated relative to healthy controls (all P<0.05). Serum Tim-3 levels were significantly lower in SLE patients with nephritis than in those SLE without nephritis (P<0.05), while no statistically significant correlation between serum IL-17 and nephritis was detected (P>0.05). Serum Tim-3 with IL-17 levels were positively correlated in SLE patients (rs=0.817, P<0.01); however, no statistically significant correlation was found between serum Tim-3 or IL-17 levels and systemic lupus erythematosus disease activity index (SLEDAI) scores in those with SLE (all P>0.05). In addition, serum Tim-3 was associated with central lesions in SLE patients, while there were no significant correlations between serum Tim-3 or IL-17 levels and other SLE clinical parameters.ConclusionsIncreased serum Tim-3 and IL-17 levels and their clinical associations in SLE patients suggest their possible role in this disease.

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FGF2 cooperates with IL-17 to promote autoimmune inflammation

Cited by 24 publications

References 40 publications

FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy

FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy

Screening of exosomal miRNAs derived from subcutaneous and visceral adipose tissues: Determination of targets for the treatment of obesity and associated metabolic disorders

Association of Serum T cell Immunoglobulin Domain and Mucin-3 and Interleukin-17 with Systemic Lupus Erythematosus

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