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FcRI-mediated thymic stromal lymphopoietin production by interleukin-4-primed human mast cells

¹ Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, Tokyo, ⁴ Laboratory of Stem Cell Therapy, the Institute of Medical Science, the University of Tokyo, Tokyo, ⁵ Dept of Immunology, Juntendo University School of Medicine, Tokyo, ⁶ Dept of Allergy and Immunology, National Research Institute for Child Health and Development, and, Tokyo, and ³ Dept of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Tochigi, Japan. ² Dept of Microbiology and Immunology, Baxter Laboratory in Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA, USA. ⁷ These authors contributed equally to the current paper.

CORRESPONDENCE: Y. Okayama, Division of Molecular Cell Immunology and Allergology, Advanced Medical Research Center, Nihon University Graduate School of Medical Science, 30-1 Oyaguchikami-machi, Itabashi-ku, Tokyo 173-8610, Japan. E-mail: yokayama{at}med.nihon-u.ac.jp

Keywords: Asthma, FcRI, human, interleukin-4, mast cells, thymic stromal lymphopoietin

Received: August 6, 2008
Accepted January 5, 2009

A significant increase of mRNA expression of thymic stromal lymphopoietin (TSLP) has been reported in the bronchial mast cells (MCs) of asthmatic subjects; however, the mechanism underlying the upregulation of TSLP mRNA and protein remains unknown.

FcRI-mediated activation of human MCs upregulated TSLP mRNA expression by 5.2±2.9-fold, while activation of the MCs using lipopolysaccharide and polyriboinosinic:polyribocytidylic acid failed to upregulate TSLP. Stimulation of MCs with interleukin (IL)-4 alone did not affect the TSLP mRNA expression, while pre-incubation of MCs with IL-4 for 48 h significantly enhanced the FcRI-mediated TSLP mRNA expression (by 53.7±15.9-fold; p<0.05) and the amount of TSLP in the cell pellets increased significantly from 23.4±4.3 pg·mL^–1 to 121.5±3.7 pg·mL^–1 (p<0.0001). However, the released TSLP was rapidly degraded by proteases that were released by MCs. We identified the population of cells expressing TSLP in the lungs of 16 asthmatic and 11 control subjects by immunohistochemistry. The percentage of TSLP-positive MCs in the total population of MCs was significantly increased in asthmatic airways (p<0.0001).

Thus, MCs are able to store TSLP intracellularly and to produce TSLP following aggregation of FcRI in the presence of IL-4.