STAT1 is involved in the pathogenesis of murine allergic rhinitis.
BACKGROUND
Signal transducer and activator of transcription (STAT) 1 signaling pathway mediates biological functions of interferon (IFN) gamma, which is a key cytokine-regulating T helper 1 (Thl) 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
STATI -/- BALB/c and wild-type (WT) mice were sensitized by intranasal administration of SEA, and their immunologic responses were examined.


RESULTS
STATI-1- 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-CD3stimulated 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-gamma.


CONCLUSIONS
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.
Hattori
Hisashi
H
Department of Microbiology, The Ohio State University, Columbus, Ohio, USA.
Rosas
Lucia E
LE
Okano
Mitsuhiro
M
Durbin
Joan E
JE
Nishizaki
Kazunori
K
Satoskar
Abhay R
AR
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology; D005260:Female; D007114:Immunization; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000235:genetics; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009299:Nasal Provocation Tests; D012221:Rhinitis, Allergic, Perennial / Q000235:genetics* / Q000276:immunology*; D050794:STAT1 Transcription Factor / Q000235:genetics*; D012550:Schistosoma mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D000947:Antigens, Helminth; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007073:Immunoglobulin E; D007371:Interferon-gamma