Reprogramming of profibrotic macrophages for treatment of bleomycin‐induced pulmonary fibrosis

Abstract: Fibrotic diseases cause organ failure that lead to ~45% of all deaths in the United States. Activated macrophages stimulate fibrosis by secreting cytokines that induce fibroblasts to synthesize collagen and extracellular matrix proteins. Although suppression of macrophage‐derived cytokine production can halt progression of fibrosis, therapeutic agents that prevent release of these cytokines (e.g., TLR7 agonists) have proven too toxic to administer systemically. Based on the expression of folate receptor β solely on activated myeloid cells, we have created a folate‐targeted TLR7 agonist (FA‐TLR7‐54) that selectively accumulates in profibrotic macrophages and suppresses fibrosis‐inducing cytokine production. We demonstrate that FA‐TLR7‐54 reprograms M2‐like fibrosis‐inducing macrophages into fibrosis‐suppressing macrophages, resulting in dramatic declines in profibrotic cytokine release, hydroxyproline biosynthesis, and collagen deposition, with concomitant increases in alveolar airspaces. Although nontargeted TLR7‐54 is lethal at fibrosis‐suppressing doses, FA‐TLR7‐54 halts fibrosis without evidence of toxicity. Taken together, FA‐TLR7‐54 is shown to constitute a novel and potent approach for treating fibrosis without causing dose‐limiting systemic toxicities.

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch

Verweise und Beziehungen

• Erschienen in: Reprogramming of profibrotic macrophages for treatment of bleomycin‐induced pulmonary fibrosis ; volume:12 ; number:8 ; year:2020 ; extent:15 ; EMBO molecular medicine / European Molecular Biology Organization ; 12, Heft 8 (2020) (gesamt 15)

Beteiligte, Orts- und Zeitangaben

• Urheber: Zhang, Fenghua ; Ayaub, Ehab A. ; Wang, Bingbing ; Puchulu‐Campanella, Estela ; Li, Yen‐Hsing ; Hettiarachchi, Suraj U. ; Lindeman, Spencer D. ; Luo, Qian ; Rout, Sasmita ; Srinivasarao, Madduri ; Cox, Abigail ; Tsoyi, Konstantin ; Nickerson‐Nutter, Cheryl ; Rosas, Ivan O. ; Low, Philip S.

Weitere Informationen

• DOI: 10.15252/emmm.202012034
• URN: urn:nbn:de:101:1-2022070408160605896564
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 15.08.2025, 07:34 MESZ