Signal transducer and activator of transcription (STAT) 1 signaling pathway mediates biological functions of interferon (IFN) γ, which is a key cytokine-regulating T helper 1 (Th1) differentiation. Although constitutive activation of STAT1 has been reported in the airway epithelium of patients with chronic asthma, its in vivo role in the pathogenesis of allergic rhinitis is not clear. We determined the role of STAT1 in the pathogenesis of allergic rhinitis in vivo using STAT1 gene-deficient (STAT1–/–) mice and a murine model of Schistosoma mansoni egg antigen (SEA)–induced allergic rhinitis.
Methods
STAT1 –/– BALB/c and wild-type (WT) mice were sensitized by intranasal administration of SEA, and their immunologic responses were examined.
Results
STAT1 –/– mice showed impaired nasal eosinophilia and markedly reduced histamine-induced nasal hyperresponsiveness after SEA sensitization. Moreover, levels of Th2-associated SEA-specific IgG1 and IgE antibodies were lower in STAT1 –/– mice. Anti-CD3–stimulated nasal lymphocytes from STAT1–/–mice also produced less amounts of Th2-associated cytokines IL-4, IL-5, IL-10, and IL-13 compared with WT mice, but both produced comparable levels of IFN-γ.
Conclusion
These results show that STAT1 is involved in the pathogenesis of SEA-induced allergic rhinitis in BALB/c mice. Furthermore, they reveal a surprising role of STAT1 in induction of nasal eosinophilia, and Th2-type cytokine production from nasal lymphocytes during allergic rhinitis.
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