Hyperexpression of FcγRI and Toll-like receptor 4 in the intestinal mast cells of Crohn’s disease patients Ryota Kobayashi a , Shinichi Okamura a, ⁎ , Tatsukuni Ohno b,c , Hirohisa Saito b,c , Masatomo Mori a , Chisei Ra d , Yoshimichi Okayama b,d, ⁎ a Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Japan b Research Unit for Allergy Transcriptome, Research Center for Allergy and Immunology, RIKEN Yokohama Institute, Yokohama, Japan c Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan d Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Sciences, Tokyo, Japan Received 20 March 2007; accepted with revision 15 July 2007 Available online 12 September 2007 Abstract We previously reported that human mast cells (MCs) express high affinity IgG receptor (FcγRI) and Toll-like receptor 4 (TLR4) in response to interferon (IFN)-γ in vitro. The number of MCs is known to increase in Crohn’s disease (CD) and ulcerative colitis (UC). We aimed to examine the expression and function of the receptors in these diseases by immunohistochemistry of the colonic mucosae and by in vitro experiments. The density of MCs expressing FcγRI, TLR4, or both proteins was significantly higher in CD than in UC or control samples. The density of TNF-α + MCs expressing FcγRI or TLR4 was significantly higher in CD than in control samples. LPS and IgG1 cross-linking synergistically induced a high level of TNF-α production in IFN-γ-treated human MCs. Hyperexpression of FcγRI and TLR4 on MCs was related to the high frequency of TNF-α expression in CD, suggesting the activation of MCs via these receptors in vivo. © 2007 Elsevier Inc. All rights reserved. KEYWORDS Crohn’s disease; Mast cells; FcγRI; Toll-like receptor 4; Tumor necrosis factor-α Introduction Mast cells (MCs) are the primary responders in allergic reactions, most of which are triggered by cross-linking of a high-affinity IgE receptor, FcεRI [1]. We have previously reported that human MCs also express a high-affinity IgG receptor, FcγRI, in response to interferon (IFN)-γ, and after aggregation of FcγRI, MCs release various mediators, such as histamine, leukotrienes, cytokines, and chemokines [2]. Aggregation of FcγRI results in a large amount of TNF-α production in human MCs [2,3]. Furthermore, we have reported that human MCs express functional Toll-like ⁎ Corresponding authors. Y. Okayama is to be contacted at Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo 173-8610, Japan. Fax: +81 339728227. S. Okamura, Department of Medical Informatics and Decision Sciences, Gunma University Hospital, 3-39- 15 Showa-machi, Maebashi 371-8511, Japan. Fax: +81272208770. E-mail addresses: sokamura@showa.gunma-u.ac.jp (S. Okamura), yokayama@med.nihon-u.ac.jp (Y. Okayama). 1521-6616/$ – see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.clim.2007.07.008 available at www.sciencedirect.com www.elsevier.com/locate/yclim Clinical Immunology (2007) 125, 149–158