Abrogation of High-Affinity IgE Receptor-Mediated Mast Cell Activation at the Effector Phase Prevents Contact Hypersensitivity to Oxazolone

作者：Kobayashi Maiko; Nunomura Satoshi; Gon Yasuhiro; Endo Daisuke; Kishiro Sachiko; Fukunaga Makiko; Kitahata Yuko; Terui Tadashi; Ra Chisei^*

来源：Journal of Investigative Dermatology, 2010, 130(3): 725-731.

DOI：10.1038/jid.2009.289

Inflammatory mediators released from mast cells (MCs) through engagement of the high-affinity receptor for IgE (Fc epsilon RI) have pivotal roles in chemical allergen-induced contact hypersensitivity (CHS) reactions, which suggests that the blockade of MC activation through Fc epsilon RI stimulation may attenuate allergic contact dermatitis (CD). To address this possibility, we employed the following two approaches: (i) modulation of Fc epsilon RI-mediated MC activation by introducing mutations in tyrosine residues of the Fc epsilon RI beta-chain immunoreceptor tyrosine-based activation motif (ITAM) and 00 blockade of Fc epsilon RI-mediated MC activation employing a recombinant soluble ecto-domain of the human Fc epsilon RI alpha-chain (rsFc epsilon RI alpha). In this study, we show that optimal MC activation through the Fc epsilon RI beta-chain ITAM has essential roles in the onset of CHS to oxazolone (Oxa), a well-characterized chemical allergen. In addition, we demonstrate that administration of the rsFc epsilon RI alpha after sensitization successfully prevents murine CHS to Oxa. In a chronic CD model elicited by multiple challenges with low-dose Oxa, application of the rsFc epsilon RI alpha during the course of the challenges showed suppressive effects on CHS to Oxa. Taken together, our data indicate that inhibition of Fc epsilon RI-dependent MC activation can suppress allergic CD.

• 出版日期2010-3