Mouse Models of Allergic Diseases: TSLP and Its Functional Roles

Abstract

The cytokine TSLP was originally identified in a murine thymic stromal cell line as a lymphoid growth factor. After the discovery of TSLP, extensive molecular genetic analyses and gene targeting experiments have demonstrated that TSLP plays an essential role in allergic diseases. In this review, we discuss the current status of TSLP and its functional role in allergic diseases particularly by focusing on effects of TSLP on haematopoietic cells in mouse models. It is our conclusion that a number of research areas, i.e., a new source of TSLP, effects of TSLP on non-haematopoietic and haematopoietic cells, synergistic interactions of cytokines including IL-25 and IL-33 and a regulation of TSLP expression and its function, are critically needed to understand the whole picture of TSLP involvement in allergic diseases. The mouse models will thus contribute further to our understanding of TSLP involvement in allergic diseases and development of therapeutic measures for human allergic diseases.

Long TSLP transcript expression and release of TSLP induced by TLR ligands and cytokines in human keratinocytes

“…Thymic stromal lymphopoietin (TSLP), a cytokine produced in response to both environmental and endogenous factors, contributes to disorders and homeostasis [1][2][3][4]. Highly expressed in keratinocytes in the lesions of atopic dermatitis patients and bronchial epithelial cells in asthma patients, TSLP plays a key role in allergic diseases through its effect on dendritic cells [5][6][7] and other types of cells [8][9][10][11].…”

Thymic stromal lymphopoietin receptor blockade reduces allergic inflammation in a cynomolgus monkey model of asthma

“…5,[9][10][11][12] In mouse models overexpression of TSLP in the lung and skin resulted in a strong T H 2-type response. 13,14 Repeated administration of TSLP into the airways of mice results in eosinophilic inflammation that can be blocked by an anti-OX40 ligand antibody, suggesting OX40 ligand upregulation in DCs is an important feature of TSLP-DC activation. 15 In addition, TSLPR knockout mice are resistant to the development of allergic inflammation in the ovalbumin model.…”

Induction of Thymic Stromal Lymphopoietin Production by Nonanoic Acid and Exacerbation of Allergic Inflammation in Mice

“…Various types of cells including epithelial cells such as keratinocytes and fibroblasts were shown to produce TSLP when stimulated with antigens, cytokines, and toll-like receptor stimulants 7, 12 . As described above, evidence has accumulated that several chemical compounds induce TSLP production.…”

“…TSLP is an IL-7-like cytokine 3 that is produced mainly by epithelial cells, and plays important roles in the regulation of immune responses by inducing the maturation and activation of dendritic cells 4, 5, 6 , lymphocytes, basophil precursors, and fibrocytes 7 . The production of TSLP is increased at inflamed sites in patients with severe asthma 5 , atopic dermatitis 8 , and allergic rhinitis 9 .…”