title: Mast cells contribute to initiation of autoantibody-mediated arthritis via IL-1.
abstract: Mast cells are immune sentinels that participate in the defense against bacteria and parasites. Resident within the joint, mast cells become activated in human rheumatoid arthritis and are implicated in the pathogenesis of experimental murine synovitis. However, their arthritogenic role remains undefined. Using a model of autoantibody-induced arthritis, we show that mast cells contribute to the initiation of inflammation within the joint by elaboration of IL-1. Mast cells become activated to produce this cytokine via the IgG immune complex receptor FcgammaRIII. Interestingly, mast cells become dispensable for the perpetuation of arthritis after delivery of IL-1, highlighting the contribution of this lineage to arthritis induction. These findings illuminate a mechanism by which mast cells can participate in the pathogenesis of autoimmune inflammatory arthritis and provide insights of potential relevance to human rheumatoid arthritis.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Binstadt
authors.forename: Paul A
authors.initials: PA
authors.lastname: Monach
authors.forename: Alyssa
authors.initials: A
authors.lastname: Johnsen
authors.forename: Michael
authors.initials: M
authors.lastname: Gurish
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Christophe
authors.initials: C
authors.lastname: Benoist
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
mesh_terms: D000818:Animals; D001168:Arthritis / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D001323:Autoantibodies; D004195:Disease Models, Animal; D007249:Inflammation / Q000209:etiology / Q000473:pathology; D007375:Interleukin-1 / Q000096:biosynthesis*; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D017452:Receptors, IgG / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D007375:Interleukin-1; D017452:Receptors, IgG