High mobility group nucleosome-binding protein 1 acts as an alarmin critical for the induction of immune response (113.7)

Abstract

Abstract Alarmins, defined as endogenous mediator(s) capable of promoting the recruitment and activation of antigen-presenting cells (APCs) including dendritic cells (DCs), can potentially promote immunity, however, their essential contribution to the induction immune responses remain to be demonstrated. Here we report the identification of HMGN1 as a novel alarmin that is critical to the induction of antigen-specific immune response. HMGN1 induced DC maturation and recruitment of APCs and activated NF-κB and multiple MAPKs, in a MyD88-dependent manner. HMGN1 promoted antigen-specific immune response upon co-administration with an antigen. Furthermore, knockout of HMGN1 in mice greatly reduced antigen-specific antibody and T cell responses upon intraperitoneal immunization with an antigen using LPS as an adjuvant. The impaired ability of HMGN1 KO 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 non-leukocytes played a more critical role in the induction of antigen-specific antibody and T cell responses. Thus, HMGN1 acts as a novel alarmin critical for the induction of adaptive immune response.