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  • Poster presentation
  • Open Access

Mast cells jump start K/BxN serum transfer arthritis via IL-1

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Arthritis Research & Therapy20079 (Suppl 3) :P6

  • Published:


  • Public Health
  • Arthritis
  • Cell Population
  • Mast Cell
  • Systemic Level

Mast cell-deficient W/Wv mice are resistant to K/BxN serum transfer arthritis, and this resistance may be overcome by engraftment with mast cells. However, the pathways by which mast cells participate in arthritis remain unknown. Using a candidate mediator approach, we explored IL-1 as a potentially key mediator by which mast cells promote arthritis. As expected, IL-1α/β-deficient mice were completely resistant to arthritis. Short-term administration of exogenous IL-1 restored an attenuated arthritis course in these animals, consistent with an ongoing requirement for IL-1. Surprisingly, deficient W/Wv mice treated with IL-1 at disease induction displayed a full normal course of arthritis, demonstrating that exogenous IL-1 can bypass the need for mast cells. TNF proved unable to exert a similar effect. We therefore engrafted IL-1-/- bone marrow-derived mast cells (BMMC) into W/Wv animals and found that these animals displayed resistance to arthritis equivalent to nonengrafted W/Wv mice, consistent with an obligate role for IL-1 of mast cell origin. Exploring further the mechanisms by which mast cells may become activated in this IgG1-driven model, we found that BMMC stimulated in vitro via FcγRIII elaborated IL-1, while BMMC lacking this receptor were unable to mediate arthritis upon engraftment into W/Wv recipients. While BMMC engrafted into W/Wv animals disproportionately populate the spleen, we excluded a contribution from this aphysiologic mast cell population via splenectomy and by documenting that systemic levels of IL-1 were not detectable during arthritis initiation in engrafted animals. We conclude that mast cells local to the joint and activated via FcγRIII promote K/BxN serum transfer arthritis by production of IL-1, an activity that appears delimited to the initiation of disease (the 'jump start').



This work was supported by grant K08 AR051321 (PAN), Cogan Family Foundation and NIH R01 AI 59746-01 (DML).

Authors’ Affiliations

Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Boston, MA, USA
Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
Institute of Medical Science, University of Tokyo, Tokyo, Japan


© BioMed Central Ltd 2007