Mast cell regulation of epithelial TSLP expression plays an important role in the development of allergic rhinitis.
Epithelial cell-derived thymic stromal lymphopoietin (TSLP) is a master switch for asthma or atopic dermatitis by inducing a dendritic cell-mediated Th2-type allergic inflammation. Allergic rhinitis is also pathologically characterized by Th2-type allergic inflammation. This study demonstrates that mast cells regulate the epithelial TSLP expression in allergic rhinitis. TSLP expression was found to be up-regulated predominantly in the nasal epithelium in the ovalbumin (OVA)-sensitized and -nasally challenged mouse model of allergic rhinitis, which was abolished in mast cell-deficient WBB6F1-W/W(v) in comparison with control WBB6F1-+/+ mice. Similarly, the epithelial TSLP expression was reduced in Fc receptor gamma chain (FcgammaR)-deficient mice, where the high-affinity IgE receptor (FcepsilonRI) is not expressed on mast cells, in comparison with control C57BL/6 mice. Furthermore, the administration of neutralizing TSLP antibody during the challenge phase of OVA inhibited the development of allergic rhinitis. These results suggest that the direct stimulation of epithelial cells by antigens alone may not be sufficient to induce TSLP expression in the nasal epithelium, and that mast cell regulation of epithelial TSLP expression, possibly via FcepsilonRI, plays an important role in the development of allergic rhinitis.
Miyata
Masanori
M
Department of Immunology, University of Yamanashi Faculty of Medicine, Yamanashi, Japan.
Hatsushika
Kyosuke
K
Ando
Takashi
T
Shimokawa
Naomi
N
Ohnuma
Yuko
Y
Katoh
Ryohei
R
Suto
Hajime
H
Ogawa
Hideoki
H
Masuyama
Keisuke
K
Nakao
Atsuhito
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D008407:Mast Cells / Q000276:immunology* / Q000637:transplantation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010047:Ovalbumin / Q000276:immunology; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012130:Respiratory Hypersensitivity / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis / Q000378:metabolism* / Q000473:pathology; D000094632:Thymic Stromal Lymphopoietin
D000906:Antibodies; D016207:Cytokines; D017452:Receptors, IgG; D010047:Ovalbumin; D019009:Proto-Oncogene Proteins c-kit; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse