Abstract
Nuclear antigens are known to trigger off innate and adaptive immune responses. Recent studies have found that the complex of nucleic acids and core histones that are derived from damaged cells may regulate allergic responses. However, no fundamental study has been performed concerning the role of linker histone H1 in mast cell-mediated type I hyperreactivity. In this study, we explored the impact of histone H1 on mast cell-mediated allergic responses both in vitro and in vivo. In the course of a bona-fide experimental allergen sensitization model upon co-injection with alum adjuvant, ovalbumin (OVA), but not PBS, induced elevated levels of circulating histone H1. Intranasal challenge with histone H1 to OVA/alum- (but not PBS/alum)-sensitized mice induced significantly severer symptoms of allergic rhinitis than those in mice sensitized and challenged with OVA. A monoclonal antibody against histone H1 not only suppressed mast cell degranulation, but also ameliorated OVA-induced nasal hyperreactivity and IgE-mediated passive cutaneous anaphylaxis. Our present data suggest that nuclear histone H1 represents an alarmin-like endogenous mediator acting on mast cells, and that its blockage has a therapeutic potential for mast cell-mediated type I hyperreactivity.
Highlights
The release of nuclear antigens from damaged cells and/or activated immune cells, such as dendritic cells (DCs) and macrophages, into the blood stream has been associated with the progression of several diseases, including infectious diseases, proinflammatory disorders, PLOS ONE | DOI:10.1371/journal.pone.0153630 April 18, 2016Histone H1 and Mast Cell-Mediated Type I Allergy
We have demonstrated the transient induction of autoantibody against histone H1 and high-mobility group box 1 (HMGB1), which may be related to long-term liver allograft acceptance [8,9,10,11]
We report for the first time the impact of linker histone H1 on the pathogenesis of mast cell-mediated allergic responses and the potential of histone H1 as a molecular target for therapeutics for mast cell-mediated type I hyperreactivity
Summary
The release of nuclear antigens from damaged cells and/or activated immune cells, such as dendritic cells (DCs) and macrophages, into the blood stream has been associated with the progression of several diseases, including infectious diseases, proinflammatory disorders, PLOS ONE | DOI:10.1371/journal.pone.0153630 April 18, 2016. We have demonstrated elevated levels of circulating histone H1 and high-mobility group box 1 (HMGB1) in the course of liver transplant rejection [6,7]. These nuclear antigens may act as alarmins in the induction of proinflammatory immune responses. A recent paper noted the significance of host cell DNA complexed with core histones, but not linker histone H1, in the initiation of a T cell-intrinsic Th2 cell differentiation by unknown innate immune mechanisms [30] It is unclear about the role of histone H1 in mast cell-mediated type I hyperreactivity. The therapeutic potential of a newly developed monoclonal Ab (mAb) against a histone H1 peptide mimotope (SSVLYGGPPSAA) referred to as SSV mAb, which is responsible for the immunosuppression of anti-histone H1 mAb [31], was evaluated
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
