Z Gastroenterol 2017; 55(08): e57-e299
DOI: 10.1055/s-0037-1604793
Kurzvorträge
Dünndarm und Dickdarm, Proktologie
CED Therapieansätze – klinisch und experimentell: Donnerstag, 14 September 2017, 09:40 – 10:52, Florenz/Forschungsforum 3
Georg Thieme Verlag KG Stuttgart · New York

Monocytic PDGFR-α expression is essential for protection against intestinal inflammation

Authors

  • C Manthey

    1   I. Medizinische Klinik und Poliklinik, Unviversitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

  • P Pelzcar

    1   I. Medizinische Klinik und Poliklinik, Unviversitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

  • A Eder

    1   I. Medizinische Klinik und Poliklinik, Unviversitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

  • S Wende

    1   I. Medizinische Klinik und Poliklinik, Unviversitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland

  • S Huber

    1   I. Medizinische Klinik und Poliklinik, Unviversitätsklinikum Hamburg-Eppendorf, Hamburg, Deutschland
Further Information

Publication History

Publication Date:
02 August 2017 (online)

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    PDGFs comprise a family of growth factors and their receptors. PDGF expression is linked to survival, proliferation and migration and is observed mainly in macrophages, endothelial cells and smooth muscle cells. The PDGF receptors are predominantly expressed by endothelial cells, epithelial cells and macrophages.

    Pathomechanisms in inflammatory bowel disease (IBD) include a disturbed innate and adaptive immune response to an altered intestinal microbiota. Proinflammatory cytokines and growth factors are involved in maintaining disease. Furthermore, proinflammatory cytokines induce expression of PDGFR-β in smooth muscle cells and promote their proliferation; possibly leading to stricture formation. PDGFR has also been found on the surface of Th22 cells with yet undefined function. There have been described opposing roles for PDGFR in influencing mucosal healing in different mouse models of intestinal inflammation.

    In conclusion, the role of PDGF/Rs in IBD pathogenesis is not well defined yet, although our data point towards a distinct function for PDGFR in intestinal macrophages.

    We found a significant induction of PDGFR-α and PDGFR-β in inflamed tissue of patients with Crohn's disease indicating a role either in disease progression or healing. Next, we sought to determine PDGFR expression in mice undergoing DSS colitis. We found a significant induction of PDGFR-α and PDGFA expression in colonic tissue. Immunohistochemistry revealed an interstitial signal for PDGFR-α indicating involvement of intestinal immune cells. We next induced DSS colitis in PDGFRfl/fl-LysM-Cre mice, thereby investigating the function of PDGFR-α in myeloid cells. PDGFR-αΔMyel mice display an aggravated phenotype of intestinal inflammation. They show significantly increased weight loss in DSS colitis as well as reduced survival compared to wild types. Interestingly, we observed that the aggravated phenotype of PDGFR-αΔMyel mice is partly transmissible on cohoused wild types that show increased weight loss compared to separately housed wild types. These data indicate that loss of PDGFR-α in macrophages leads to an altered intestinal microbiota resulting in increased vulnerability towards intestinal inflammation, this hypothesis is supported by analysis of 16 s rRNA.