Differential role of thymic stromal lymphopoietin in the induction of airway hyperreactivity and Th2 immune response in antigen-induced asthma with respect to natural killer T cell function.

Abstract

Asthma is an inflammatory lung disease, in which CD1d-restricted natural killer T (NKT) cells play an important pathogenic role. Also, recent reports indicated that a cytokine, thymic stromal lymphopoietin (TSLP), is essential for the development of antigen-induced asthma. Here we examined the relationship between NKT cells and TSLP in a mouse model of asthma. NKT cells express TSLP receptor as well as IL-7 receptor alpha-chain. TSLP acts on NKT cells to preferentially increase their IL-13 production but not IFN-gamma and IL-4. In an allergen-induced asthma model, the development of airway hyperreactivity, a cardinal feature of asthma, was increased in TSLP transgenic mice, whereas this effect was not observed in TSLP transgenic mice lacking NKT cells. Interestingly, in the NKT cell-lacking TSLP transgenic mice, pulmonary eosinophilia and increase in IgE did not improve. Pulmonary lymphocytes from the NKT cell-lacking TSLP transgenic mice produced much less IL-13 upon CD3 stimulation than those from NKT cell-competent TSLP transgenic mice. These resultssuggest that, in allergen-induced asthma, TSLP acts on NKT cells to enhance airway hyperreactivity by upregulating their IL-13 production, whereas eosinophilia and IgE production are not influenced.

• Authors: Yuko Nagata, Hajime Kamijuku, Masaru Taniguchi, Steven Ziegler, Ken-ichiro Seino
• Journal: International archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 144 Issue 4 Pg. 305-14 ( 2007) ISSN: 1423-0097 [Electronic] Switzerland
• PMID: 17652941 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2007 S. Karger AG, Basel.

Chemical References

• Cytokines
• Immunoglobulins
• RNA, Messenger
• Receptors, Cytokine
• Recombinant Proteins
• Tslpr protein, mouse
• Immunoglobulin E
• Ovalbumin
• Thymic Stromal Lymphopoietin
• TSLP protein, mouse

Topics

• Animals
• Asthma (chemically induced, immunology, physiopathology)
• Bronchial Hyperreactivity (chemically induced, immunology, physiopathology)
• Bronchoalveolar Lavage Fluid (cytology)
• Cell Proliferation (drug effects)
• Cytokines (genetics, immunology, pharmacology)
• Immunoglobulin E (blood, immunology)
• Immunoglobulins
• Killer Cells, Natural (cytology, drug effects, immunology)
• Lung (immunology, pathology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• Ovalbumin (immunology)
• RNA, Messenger (metabolism)
• Receptors, Cytokine (genetics, metabolism)
• Recombinant Proteins (immunology, pharmacology)
• Th2 Cells (immunology)
• Thymic Stromal Lymphopoietin