Thymic stromal lymphopoietin

Thymic stromal lymphopoietin (TSLP) is a protein belonging to the is_associated_with::cytokine family. It is known to play an important role in the maturation of is_associated_with::T cell populations through activation of antigen presenting cells.

TSLP is produced mainly by non-hematopoietic cells such as is_associated_with::fibroblasts, epithelial cells and different types of stromal or stromal-like cells. These cells are located in regions where TSLP activity is required.

Gene ontology
TSLP production has been observed in various species, including humans and mice. In humans TSLP is encoded by the TSLP is_associated_with::gene. is_associated_with::Alternative splicing of this gene results in two transcript variants.

Function
It mainly impacts myeloid cells and induces the release of is_associated_with::T cell-attracting chemokines from is_associated_with::monocytes and enhances the maturation of myeloid (CD11c+) dendritic cells. TSLP has also been shown to activate the maturation of a specific subset of dendritic cells located within the epidermis, called is_associated_with::Langerhans cells. Within the is_associated_with::thymus TSLP activation of both myeloid and plasmacytoid (CD123+) dendritic cells results in the production of is_associated_with::regulatory T cells.

Signalling
TSLP signals through a heterodimeric receptor complex composed of the thymic stromal lymphopoietin receptor is_associated_with::CRLF2 and the IL-7R alpha chain. After binding is_associated_with::STAT5 phosphorylation is induced resulting in the expression of upstream is_associated_with::transcription factors.

Disease
TSLP expression is linked to many disease states including asthma, inflammatory arthritis, atopic dermatitis, and eczema and other allergic states. The factors inducing the activation of TSLP release are not clearly defined.

Asthma
Expression of TSLP is enhanced under is_associated_with::asthma-like conditions (aka Airway HyperResponsiveness or AHR model in the mouse), conditioning APCs in order to orient the differentiation of T cells coming into the lungs towards a TH2 profile (T helper 2 pathway). The TH2 cells then release factors promoting an inflammatory reaction following the repeated contact with a specific antigen in the airways.

Atopic dermatitis
TSLP-activated Langerhans cells of the epidermis induce the production of is_associated_with::pro-inflammatory cytokines like is_associated_with::TNF-alpha by T cells potentially causing is_associated_with::atopic dermatitis. It is thought that understanding the mechanism of TSLP production and those potential substances that block the production, one may be able to prevent or treat conditions of asthma and/or eczema.