title: Remission of food allergy by the Janus kinase inhibitor ruxolitinib in mice.
abstract: To clarify the role of Janus kinase (JAK) in and the efficacy of JAK inhibitors on food allergy, we investigated the effect of the clinically available JAK inhibitor ruxolitinib on mouse food allergy and the functions of cultured mast cells in vitro. Anaphylactic symptoms including diarrhea and decreases in body temperature pursuant to oral ovalbumin (OVA) challenges in food allergy mice were attenuated by the daily oral administration of ruxolitinib. This drug inhibited increases in mouse mast cell protease-1 concentrations in the serum and mast cell numbers in the intestines of these mice as well as degranulation, IL-13 production, and the spontaneous and IL-9-dependent survival of mouse bone marrow-derived mast cells in spite of the absence of an effect of ruxolitinib on passive systemic anaphylaxis. Anti-OVA IgG2a, IgE, and IgG1 serum levels and the release of IFN-γ, IL-4, IL-9, and IL-10 from the OVA-restimulated splenocytes of food allergy mice were also decreased by the treatment. Moreover, ruxolitinib administration to mice that had already exhibited anaphylactic responses to previous challenges reduced anaphylactic responses to further oral OVA challenges, which suggested that ruxolitinib has a therapeutic potential on food allergy. Our results showed that ruxolitinib remitted food allergy in mice mainly through immunosuppression and the prevention of mast cell hyperplasia, and partially through the inhibition of mast cell activation. We consider JAK inhibition to be a promising strategy for the prevention of food allergy, and ruxolitinib along with its derivatives inhibiting JAK as good candidates for therapeutic drugs to treat food allergy.
authors: Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Hyogo 658-8558, Japan. Electronic address: yam@kobepharma-u.ac.jp.
authors: Kouya
authors: K
authors: Yamaki
authors: Department of Pharmacology, Kobe Pharmaceutical University, Kobe, Hyogo 658-8558, Japan. Electronic address: yoshino@kobepharma-u.ac.jp.
authors: Shin
authors: S
authors: Yoshino
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002460:Cell Line; D053818:Chymases / Q000097:blood; D016207:Cytokines / Q000276:immunology; D005512:Food Hypersensitivity / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D020397:Goblet Cells / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007422:Intestines / Q000166:cytology; D053612:Janus Kinases / Q000037:antagonists & inhibitors*; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009570:Nitriles; D010047:Ovalbumin / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D013154:Spleen / Q000166:cytology
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D007073:Immunoglobulin E; C540383:ruxolitinib; D010047:Ovalbumin; D053612:Janus Kinases; D053818:Chymases; C509230:Mcpt1 protein, mouse
keywords: Anaphylaxis; BMMCs; FA; Food allergy; JAK; Janus kinase; MCs; MMCP; Mast cells; OVA; PSA; Ruxolitinib; STAT; Tr; bone marrow-derived mast cells; food allergy; mast cells; mouse mast cell protease; ovalbumin; passive systemic anaphylaxis; regulatory T cell type; signal transducer and activator of transcription