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FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice

Author

Listed:
  • Madeleen Bosma

    (Karolinska Institutet)

  • Marco Gerling

    (Center of Innovative Medicine, Karolinska Institutet)

  • Jenny Pasto

    (Karolinska Institutet)

  • Anastasia Georgiadi

    (Karolinska Institutet)

  • Evan Graham

    (Karolinska Institutet)

  • Olga Shilkova

    (Karolinska Institutet)

  • Yasunori Iwata

    (Kanazawa University Hospital)

  • Sven Almer

    (Solna, Karolinska Institutet, and Karolinska University Hospital
    GastroCentrum, Karolinska University Hospital)

  • Jan Söderman

    (Ryhov County Hospital)

  • Rune Toftgård

    (Center of Innovative Medicine, Karolinska Institutet)

  • Fredrik Wermeling

    (Solna, Karolinska Institutet, and Karolinska University Hospital)

  • Elisabeth Almer Boström

    (Karolinska Institutet)

  • Pontus Almer Boström

    (Karolinska Institutet)

Abstract

FNDC4 is a secreted factor sharing high homology with the exercise-associated myokine irisin (FNDC5). Here we report that Fndc4 is robustly upregulated in several mouse models of inflammation as well as in human inflammatory conditions. Specifically, FNDC4 levels are increased locally at inflamed sites of the intestine of inflammatory bowel disease patients. Interestingly, administration of recombinant FNDC4 in the mouse model of induced colitis markedly reduces disease severity compared with mice injected with a control protein. Conversely, mice lacking Fndc4 develop more severe colitis. Analysis of binding of FNDC4 to different immune cell types reveals strong and specific binding to macrophages and monocytes. FNDC4 treatment of bone marrow-derived macrophages in vitro results in reduced phagocytosis, increased cell survival and reduced proinflammatory chemokine expression. Hence, treatment with FNDC4 results in a state of dampened macrophage activity, while enhancing their survival. Thus, we have characterized FNDC4 as a factor with direct therapeutic potential in inflammatory bowel disease and possibly other inflammatory diseases.

Suggested Citation

  • Madeleen Bosma & Marco Gerling & Jenny Pasto & Anastasia Georgiadi & Evan Graham & Olga Shilkova & Yasunori Iwata & Sven Almer & Jan Söderman & Rune Toftgård & Fredrik Wermeling & Elisabeth Almer Bost, 2016. "FNDC4 acts as an anti-inflammatory factor on macrophages and improves colitis in mice," Nature Communications, Nature, vol. 7(1), pages 1-13, September.
  • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11314
    DOI: 10.1038/ncomms11314
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    Cited by:

    1. Xin Zhang & Yi-Peng Gao & Wen-Sheng Dong & Kang Li & Yu-Xin Hu & Yun-Jia Ye & Can Hu, 2024. "FNDC4 alleviates cardiac ischemia/reperfusion injury through facilitating HIF1α-dependent cardiomyocyte survival and angiogenesis in male mice," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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