About TSLP:
TSLP stands for Thymic Stromal Lymphopoietin. It is a cytokine protein often linked to T Cell maturation and antigen presenting cells. It is mainly produced by stromal cells, along with various hematopoietic cells. All of these cells are found in parts of the body that require TSLP activity.
Mechanism/Interactions
TSLP primarily interacts with myeloid cells in the body. From here, it triggers chemokine production from monocytes. These chemokines are known to attract T-cells to the area. TSLP also works to improve how well myeloid dendritic cells mature as well.
Furthermore, TSLP has also been proven to interact with various dendritic cells found in the epidermis. These cells are known as Langerhans cells, and TSLP helps with their maturation too.
Regulatory T cells are produced in the thymus due to TSLP. It helps activate myeloid and plasmacytoid dendritic cells, which leads to T cell production.
TSLP passes signals through a heterodimeric receptor complex. This is formed out of CRLF2 (a thymic stromal lymphopoietin receptor) and an alpha chain known as IL-7R. Once the binding is complete, this results in the induction of STAT5 phosphorylation. Accordingly, transcription factors are expressed.
Function
TSLP activates antigen presenting cells to help mature the T cell population in the body. This cytokine protein is responsible for promoting cellular responses that are linked to immunity, in multiple diseases. It has been strongly linked to inflammation, allergic inflammation, asthma, chronic obstructive pulmonary disease, eczema, arthritis, esophagitis, and many more.It is still unknown what factors are present to induce the activation of TSLP release in the cells.
T cells are an essential part of the immune system and can help treat and prevent diseases like the ones mentioned above. As a consequence, the TSLP protein has been thought of as a potential treatment for these types of diseases. It works to increase the number of local T cells in an afflicted area. Studies have shown that TSLP is expressed in abundance in the lungs when asthma-like circumstances are present. It matures the T cells, which work to release an inflammatory response in the airways.
Through further research into TSLP and the factors affecting its induction, it is believed that common conditions like asthma or eczema can be prevented.
Structure
The TSLP structure in humans is known as the TSLP receptor complex. Here, a heterodimer of TSLPR and IL-7R a are present. By looking at the structure of TSLP, you will see that it establishes a working relationship with both TSLPR and IL-7R to result in membrane-proximal receptor contacts read for signalling on an intracellular level. There must be a bond between TSLP and TSLPR for IL-7Ra to be recruited. When TSLP is stimulated, this works to activate STAT5, along with other pathways.
TSLP is often referred to as the meeting point of the cytokine-receptor interfaces. When found in humans, TSLP will activate DCs, promote the survival of all cells, and helps with the secretion of various chemokines.