Thymic stromal lymphopoietin (TSLP) is a protein belonging to the cytokine

Cytokine

Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

 family. It is known to play an important role in the maturation of T cell

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

 populations through activation of antigen presenting cells

Antigen-presenting cell

An antigen-presenting cell or accessory cell is a cell that displays foreign antigen complexes with major histocompatibility complex on their surfaces. T-cells may recognize these complexes using their T-cell receptors...

.

TSLP is produced mainly by non-hematopoietic

Haematopoiesis

Haematopoiesis is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells...

 cells such as fibroblasts, epithelial cells

Epithelium

Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...

 and different types of stromal

Stromal cell

In cell biology, stromal cells are connective tissue cells of any organ, for example in the uterine mucosa , prostate, bone marrow, and the ovary. They are cells that support the function of the parenchymal cells of that organ...

 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 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

. Alternative splicing

Alternative splicing

Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 of this gene results in two transcript variants.

Function

It mainly impacts myeloid cells and induces the release of T cell

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

-attracting chemokines from monocyte

Monocyte

Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

s and enhances the maturation of myeloid (CD11c+) dendritic cells. TSLP has also been shown to activate maturation of specific subset of dendritic cells located within the epidermis, Langerhans cell

Langerhans cell

Langerhans cells are dendritic cells of the skin and mucosa, and contain large granules called Birbeck granules. They are present in all layers of the epidermis, but are most prominant in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as...

. Within the thymus

Thymus

The thymus is a specialized organ of the immune system. The thymus produces and "educates" T-lymphocytes , which are critical cells of the adaptive immune system....

 TSLP activation of both myeloid and plasmacytoid (CD123+) dendritic cells results in the production of regulatory T cell

Regulatory T cell

Regulatory T cells , sometimes known as suppressor T cells, are a specialized subpopulation of T cells which suppresses activation of the immune system and thereby maintains tolerance to self-antigens. The existence of regulatory T cells was the subject of significant controversy among...

s.

Signalling

TSLP signals through a heterodimeric receptor complex composed of the thymic stromal lymphopoietin receptor and the IL-7R alpha

Interleukin-7 receptor-α

Interleukin-7 receptor subunit alpha also known as CD127 is a protein that in humans is encoded by the IL7R gene....

 chain. After binding STAT5

STAT5

STAT5 refers to two highly related proteins, STAT5A and STAT5B, which are encoded by separate genes, but are 90% identical at the amino acid level....

 phosphorylation is induced resulting in the expression of downstream 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 asthma

Asthma

Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...

-like conditions (aka Airway HyperResponsiveness or AHR model in the mouse), conditioning APCs in order to orientate the differentiation of T cells coming into the lungs towards a TH2

T helper cell

T helper cells are a sub-group of lymphocytes, a type of white blood cell, that play an important role in the immune system, particularly in the adaptive immune system. These cells have no cytotoxic or phagocytic activity; they cannot kill infected host cells or pathogens. Rather, they help other...

 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 .

Dermatitis

TSLP activated Langerhan cells of the epidermis induce the production of pro-inflammatory cytokines like TNF-alpha by T cells potentially causing atopic dermatitis

Atopic dermatitis

Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...

.

Eczema

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.