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High-mobility group nucleosome-binding protein 1 acts as an alarmin and is critical for lipopolysaccharideinduced immune responses

Journal of Experimental Medicine, ISSN: 0022-1007, Vol: 209, Issue: 1, Page: 157-171
2012
  • 125
    Citations
  • 0
    Usage
  • 85
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    125
  • Captures
    85
  • Mentions
    1
    • News Mentions
      1
      • News
        1

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Polypeptides for Stimulation of Immune Response Adjuvants

HMGN polypeptides belong to the high mobility group HMG family of chromosomal binding peptides. HMGN polypeptides typically function inside the cell nucleus to bind to DNA and nucleosomes and regulate the transcription of various genes. HMGN polypeptides a...

Article Description

Alarmins are endogenous mediators capable of promoting the recruitment and activation of antigen-presenting cells (APCs), including dendritic cells (DCs), that can potentially alert host defense against danger signals. However, the relevance of alarmins to the induction of adaptive immune responses remains to be demonstrated. In this study, we report the identification of HMGN1 (high-mobility group nucleosome-binding protein 1) as a novel alarmin and demonstrate that it contributes to the induction of antigen-specific immune responses. HMGN1 induced DC maturation via TLR4 (Toll-like receptor 4), recruitment of APCs at sites of injection, and activation of NF-κB and multiple mitogen-activated protein kinases in DCs. HMGN1 promoted antigen-specific immune response upon co-administration with antigens, and Hmgn1 mice developed greatly reduced antigen-specific antibody and T cell responses when immunized with antigens in the presence of lipopolysaccharide (LPS). The impaired ability of Hmgn1 mice to mount antigen-specific immune responses was accompanied by both deficient DC recruitment at sites of immunization and reduced production of inflammatory cytokines. Bone marrow chimera experiments revealed that HMGN1 derived from nonleukocytes was critical for the induction of antigen-specific antibody and T cell responses. Thus, extracellular HMGN1 acts as a novel alarmin critical for LPS-induced development of innate and adaptive immune responses.

Bibliographic Details

Yang, De; Postnikov, Yuri V.; Li, Yana; Tewary, Poonam; de la Rosa, Gonzalo; Wei, Feng; Klinman, Dennis; Gioannini, Theresa; Weiss, Jerrold P.; Furusawa, Takashi; Bustin, Michael; Oppenheim, Joost J.

Faculty Opinions Ltd

Medicine; Immunology and Microbiology

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