CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury

• Type of Material: Article
• Authors: Hirokuni Akahori, Emory University; Vinit Karmali, Emory University; Rohini Polavarapu, Emory University; Alicia Lyle, Emory University; Daiana Weiss, Emory University; Eric Shin, Emory University; Ahsan Husain, Emory University; Nawazish Naqvi, Emory University; Richard Van Dam, Emory University; Anwer Habib, Emory University; Cheol Ung Choi, Emory University; Adrienne L. King, Kennesaw State University; Kimberly Pachura, Emory University; W Robert Taylor, Emory University; David J. Lefer, LSU Health Sciences Center; Aloke Finn, Emory University
• Language: English
• Date: 2015-08-01
• Publisher: Nature Publishing Group: Nature Communications
• Publication Version: Final Published Version
• Copyright Statement: Copyright © 2015, Rights Managed by Nature Publishing Group.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/ncomms8792
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 6
• Start Page: 7792
• End Page: 7792
• Grant/Funding Information: This study is supported by an American Heart Association Grant-In-Aid, from the Woodruff Sciences Health Center at Emory University, and from the Carlyle Fraser Heart Center at Emory Hospital Midtown.; CC is supported by a grant from the CardioVascular Research Foundation, Korea (CVRF).
• Keywords: Multidisciplinary Sciences; MACROPHAGE POLARIZATION; ACTIVATION; NF-KAPPA-B; Science & Technology - Other Topics; NOTCH; (TNF)-LIKE WEAK INDUCER; SKELETAL-MUSCLE; Science & Technology; SIGNALING PATHWAYS; GROWTH; APOPTOSIS TWEAK; SCAVENGER RECEPTOR
• Research Categories: Health Sciences, Rehabilitation and Therapy; Engineering, Biomedical; Health Sciences, General

Abstract

Macrophages are an essential component of the immune response to ischaemic injury and play an important role in promoting inflammation and its resolution, which is necessary for tissue repair. The type I transmembrane glycoprotein CD163 is exclusively expressed on macrophages, where it acts as a receptor for haemoglobin:haptoglobin complexes. An extracellular portion of CD163 circulates in the blood as a soluble protein, for which no physiological function has so far been described. Here we show that during ischaemia, soluble CD163 functions as a decoy receptor for TWEAK, a secreted pro-inflammatory cytokine of the tumour necrosis factor family, to regulate TWEAK-induced activation of canonical nuclear factor-? B (NF-? B) and Notch signalling necessary for myogenic progenitor cell proliferation. Mice with deletion of CD163 have transiently elevated levels of TWEAK, which stimulate muscle satellite cell proliferation and tissue regeneration in their ischaemic and non-ischaemic limbs. These results reveal a role for soluble CD163 in regulating muscle regeneration after ischaemic injury.