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Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo

Author

Listed:
  • Michelle Reed

    (University of Michigan)

  • Anny-Claude Luissint

    (University of Michigan)

  • Veronica Azcutia

    (University of Michigan)

  • Shuling Fan

    (University of Michigan)

  • Monique N. O’Leary

    (University of Michigan)

  • Miguel Quiros

    (University of Michigan)

  • Jennifer Brazil

    (University of Michigan)

  • Asma Nusrat

    (University of Michigan)

  • Charles A. Parkos

    (University of Michigan)

Abstract

CD47 is a ubiquitously expressed transmembrane glycoprotein that regulates inflammatory responses and tissue repair. Here, we show that normal mice treated with anti-CD47 antibodies, and Cd47-null mice have impaired intestinal mucosal wound healing. Furthermore, intestinal epithelial cell (IEC)-specific loss of CD47 does not induce spontaneous immune-mediated intestinal barrier disruption but results in defective mucosal repair after biopsy-induced colonic wounding or Dextran Sulfate Sodium (DSS)-induced mucosal damage. In vitro analyses using primary cultures of CD47-deficient murine colonic IEC or human colonoid-derived IEC treated with CD47-blocking antibodies demonstrate impaired epithelial cell migration in wound healing assays. Defective wound repair after CD47 loss is linked to decreased epithelial β1 integrin and focal adhesion signaling, as well as reduced thrombospondin-1 and TGF-β1. These results demonstrate a critical role for IEC-expressed CD47 in regulating mucosal repair and raise important considerations for possible alterations in wound healing secondary to therapeutic targeting of CD47.

Suggested Citation

  • Michelle Reed & Anny-Claude Luissint & Veronica Azcutia & Shuling Fan & Monique N. O’Leary & Miguel Quiros & Jennifer Brazil & Asma Nusrat & Charles A. Parkos, 2019. "Epithelial CD47 is critical for mucosal repair in the murine intestine in vivo," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12968-y
    DOI: 10.1038/s41467-019-12968-y
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    Cited by:

    1. Arturo Raya-Sandino & Kristen M. Lozada-Soto & Nandhini Rajagopal & Vicky Garcia-Hernandez & Anny-Claude Luissint & Jennifer C. Brazil & Guiying Cui & Michael Koval & Charles A. Parkos & Shikha Nangia, 2023. "Claudin-23 reshapes epithelial tight junction architecture to regulate barrier function," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. Sungmin Moon & Seunghan Han & In-Hwan Jang & Jaechan Ryu & Min-Seok Rha & Hyung-Ju Cho & Sang Sun Yoon & Ki Taek Nam & Chang-Hoon Kim & Man-Seong Park & Je Kyung Seong & Won-Jae Lee & Joo-Heon Yoon & , 2024. "Airway epithelial CD47 plays a critical role in inducing influenza virus-mediated bacterial super-infection," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Eun-Kyung Choi & Thekkelnaycke M. Rajendiran & Tanu Soni & Jin-Ho Park & Luisa Aring & Chithra K. Muraleedharan & Vicky Garcia-Hernandez & Nobuhiko Kamada & Linda C. Samuelson & Asma Nusrat & Shigeki , 2024. "The manganese transporter SLC39A8 links alkaline ceramidase 1 to inflammatory bowel disease," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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