HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs

• Published in: Cellular immunology 2020-10, Vol.356, p.104192-104192, Article 104192
• Main Authors: Li, Ruiting, Zhang, Jiancheng, Pan, Shangwen, Yuan, Yin, Qi, Hong, Shu, Huaqing, Hu, Yingying, Ren, Lehao, Jiang, Yongxiang, Yuan, Shiying
• Format: Article
• Language: English
• Subjects: Acute lung injury; Acute Lung Injury - immunology; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Animals; Cytokines - metabolism; Disease Models, Animal; HMGB1; HMGB1 Protein - immunology; HMGB1 Protein - metabolism; HMGB1 Protein - physiology; Interleukin-10 - immunology; Lipopolysaccharides - pharmacology; Lung - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Transforming Growth Factor beta - metabolism; Treg
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1016/j.cellimm.2020.104192

•HMGB1 aggravates acute lung injury by suppressing immunosuppressive function of Tregs.•HMGB1 reduces the number and activity of Tregs.•HMGB1 reduces the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs.•Tregs stimulated by HMGB1 regulate the macrophage polarization, as well as the proinflammatory response of macrophages. CD4+CD25+FoxP3+ T helper cells (Tregs), a subgroup of CD4+ T helper cells, are critical effectors that protect against acute lung injury (ALI) by contact-dependent suppression or releasing anti-inflammatory cytokines including interleukin-10 (IL-10), and transforming growth factor (TGF-β). HMGB1 (High mobility group box 1 protein) was identified as a nuclear non-histone DNA-binding chromosomal protein, which participates in the regulation of lung inflammatory response and pathological processes in ALI. Previous studies have suggested that Tregs overexpresses the HMGB1-recognizing receptor. However, the interaction of HMGB1 with Tregs in ALI is still unclear. To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs. Anti-HMGB1 antibody and recombinant mouse HMGB1 (rHMGB1) were administered in lipopolysaccharide (LPS)-induced ALI mice and polarized LPS-primed Tregs in vitro. The Tregs pre-stimulated with or without rHMGB1 were adoptively transferred to ALI mice and depleted by Diphtheria toxin (DT). For coculture experiment, isolated Tregs were first pre-stimulated with or without rHMGB1 or anti-HMGB1 antibody, then they were cocultured with bone marrow-derived macrophages (BMMs) under LPS stimulation. Tregs protected against acute lung pathological injury. HMGB1 modulated the suppressive function of Tregs as follows: reduction in the number of the cells and the activity of Tregs, the secretion of anti-inflammatory cytokines (IL-10, TGF-β) from Tregs, the production of IL-2 from CD4+ T cells and CD11c+ DCs, and the M2 polarization of macrophages, as well as inducing proinflammatory response of macrophages. HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs.