Thymic stromal lymphopoietin
Overview
Thymic Stromal Lymphopoietin (TSLP) is a cytokine that plays a crucial role in the regulation of immune responses. It is primarily produced by epithelial cells and has significant implications in the pathogenesis of various allergic and inflammatory diseases.
Structure
TSLP is a member of the cytokine family and is structurally similar to interleukin-7 (IL-7). It is a small protein that consists of a four-helix bundle, which is a common structural motif among cytokines. The image on the right illustrates the three-dimensional structure of TSLP, highlighting its helical configuration.
Function
TSLP is involved in the activation and maturation of dendritic cells, which are essential for initiating adaptive immune responses. It acts by binding to a heterodimeric receptor complex composed of the TSLP receptor (TSLPR) and the interleukin-7 receptor alpha chain (IL-7R_). This interaction leads to the activation of downstream signaling pathways that influence the behavior of various immune cells, including T cells, B cells, and mast cells.
Role in Disease
TSLP has been implicated in the pathogenesis of several allergic diseases, such as asthma, atopic dermatitis, and allergic rhinitis. It is known to promote the differentiation of naive T cells into T helper 2 cells (Th2), which are associated with allergic inflammation. Elevated levels of TSLP have been observed in the tissues of patients with these conditions, suggesting its role as a key mediator of allergic responses.
Therapeutic Implications
Given its involvement in allergic and inflammatory diseases, TSLP is a potential target for therapeutic intervention. Several biologic agents that inhibit TSLP signaling are currently under investigation in clinical trials. These therapies aim to reduce the inflammatory response by blocking the interaction between TSLP and its receptor, thereby alleviating symptoms in patients with allergic diseases.
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Contributors: Prab R. Tumpati, MD