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

Madeleen Bosma (), Marco Gerling, Jenny Pasto, Anastasia Georgiadi, Evan Graham, Olga Shilkova, Yasunori Iwata, Sven Almer, Jan Söderman, Rune Toftgård, Fredrik Wermeling, Elisabeth Almer Boström and Pontus Almer Boström
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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
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

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms11314

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