Inflammation and tissue regeneration follow tissue damage, but little is known about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) is a nuclear protein that, when released on injury, triggers inflammation. We previously showed that HMGB1 with reduced cysteines is a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine. Here we report that fully reduced HMGB1 orchestrates muscle and liver regeneration via CXCR4, whereas disulfide HMGB1 and its receptors TLR4/MD-2 and RAGE (receptor for advanced glycation end products) are not involved. Injection of HMGB1 accelerates tissue repair by acting on resident muscle stem cells, hepatocytes, and infiltrating cells. The nonoxidizable HMGB1 mutant 3S, in which serines replace cysteines, promotes muscle and liver regeneration more efficiently than the wildtype protein and without exacerbating inflammation by selectively interacting with CXCR4. Overall, our results show that the reduced form of HMGB1 coordinates tissue regeneration and suggest that 3S may be used to safely accelerate healing after injury in diverse clinical contexts.

High mobility group box 1 orchestrates tissue regeneration via CXCR4 / M. Tirone, N.L. Tran, C. Ceriotti, A. Gorzanelli, M. Canepari, R. Bottinelli, A. Raucci, S. di Maggio, C. Santiago, M. Mellado, M. Saclier, S. François, G. Careccia, M. He, F. De Marchis, V. Conti, S.B. Larbi, S. Cuvellier, M. Casalgrandi, A. Preti, B. Chazaud, Y. Al-Abed, G. Messina, G. Sitia, S. Brunelli, M.E. Bianchi, E. Vénéreau. - In: JOURNAL OF EXPERIMENTAL MEDICINE. - ISSN 0022-1007. - 215:1(2018 Jan), pp. 303-318.

High mobility group box 1 orchestrates tissue regeneration via CXCR4

M. Saclier;G. Messina;
2018-01

Abstract

Inflammation and tissue regeneration follow tissue damage, but little is known about how these processes are coordinated. High Mobility Group Box 1 (HMGB1) is a nuclear protein that, when released on injury, triggers inflammation. We previously showed that HMGB1 with reduced cysteines is a chemoattractant, whereas a disulfide bond makes it a proinflammatory cytokine. Here we report that fully reduced HMGB1 orchestrates muscle and liver regeneration via CXCR4, whereas disulfide HMGB1 and its receptors TLR4/MD-2 and RAGE (receptor for advanced glycation end products) are not involved. Injection of HMGB1 accelerates tissue repair by acting on resident muscle stem cells, hepatocytes, and infiltrating cells. The nonoxidizable HMGB1 mutant 3S, in which serines replace cysteines, promotes muscle and liver regeneration more efficiently than the wildtype protein and without exacerbating inflammation by selectively interacting with CXCR4. Overall, our results show that the reduced form of HMGB1 coordinates tissue regeneration and suggest that 3S may be used to safely accelerate healing after injury in diverse clinical contexts.
immunology and allergy; immunology
Settore BIO/17 - Istologia
JOURNAL OF EXPERIMENTAL MEDICINE
Article (author)
File in questo prodotto:
File Dimensione Formato  
JEM Tirone 2017.pdf

accesso aperto

3.41 MB Adobe PDF Visualizza/Apri
303.full.pdf

accesso aperto

3.39 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/549903
Citazioni
  • ???jsp.display-item.citation.pmc??? 53
  • Scopus 76
  • ???jsp.display-item.citation.isi??? 78
social impact