HMGB1 aggravates lipopolysaccharide-induced acute lung injury through suppressing the activity and function of Tregs.
Cell Immunol
; 356: 104192, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32853967
ABSTRACT
BACKGROUND:
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-ß). 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.OBJECTIVE:
To investigate whether HMGB1 aggravates ALI by suppressing immunosuppressive function of Tregs.METHODS:
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.RESULTS:
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-ß) 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.CONCLUSIONS:
HMGB1 could aggravate LPS induced-ALI through suppressing the activity and function of Tregs.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Reguladores
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Proteína HMGB1
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Lesão Pulmonar Aguda
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article