title: CD163 interacts with TWEAK to regulate tissue regeneration after ischaemic injury.
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-κB (NF-κB) 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.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Hirokuni
authors.initials: H
authors.lastname: Akahori
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Vinit
authors.initials: V
authors.lastname: Karmali
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Rohini
authors.initials: R
authors.lastname: Polavarapu
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Alicia N
authors.initials: AN
authors.lastname: Lyle
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Daiana
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Shin
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Ahsan
authors.initials: A
authors.lastname: Husain
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Nawazish
authors.initials: N
authors.lastname: Naqvi
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Van Dam
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Anwer
authors.initials: A
authors.lastname: Habib
authors.affiliation: 1] Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA [2] Division of Cardiology, Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul 152-703, Republic of Korea.
authors.forename: Cheol Ung
authors.initials: CU
authors.lastname: Choi
authors.affiliation: Kennesaw State University Department of Ecology, Evolution, and Organismal Biology Kennesaw, Georgia 30144, USA.
authors.forename: Adrienne L
authors.initials: AL
authors.lastname: King
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Pachura
authors.affiliation: 1] Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA [2] Atlanta VA Medical Center, Atlanta, Georgia 30033, USA [3] Coulter Department of Biomedical Engineering at Georgia Tech and Emory, Atlanta, Georgia 30332, USA.
authors.forename: W Robert
authors.initials: WR
authors.lastname: Taylor
authors.affiliation: LSU Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Lefer
authors.affiliation: Department of Internal Medicine, Division of Cardiology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Aloke V
authors.initials: AV
authors.lastname: Finn
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D000074049:Cytokine TWEAK; D008264:Macrophages / Q000502:physiology*; D008297:Male; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D011897:Random Allocation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D051880:Receptors, Notch / Q000378:metabolism; D012038:Regeneration; D015427:Reperfusion Injury; D048069:Tumor Necrosis Factors / Q000378:metabolism*; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D000074049:Cytokine TWEAK; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D051880:Receptors, Notch; C491645:Tnfsf12 protein, mouse; D048069:Tumor Necrosis Factors