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.