TSLP as druggable target - a silver-lining for atopic diseases?

Pharmacol Ther. 2021 Jan:217:107648. doi: 10.1016/j.pharmthera.2020.107648. Epub 2020 Aug 3.

Abstract

Atopic diseases refer to common allergic inflammatory diseases such as atopic dermatitis (AD), allergic rhinitis (AR), and allergic asthma (AA). AD often develops in early childhood and may herald the onset of other allergic disorders such as food allergy (FA), AR, and AA. This progression of the disease is also known as the atopic march, and it goes hand in hand with a significantly impaired quality of life as well as a significant economic burden. Atopic diseases usually are considered as T helper type 2 (Th2) cell-mediated inflammatory diseases. Thymic stromal lymphopoietin (TSLP), an epithelium-derived pro-inflammatory cytokine, activates distinct immune and non-immune cells. It has been shown to be a master regulator of type 2 immune responses and atopic diseases. In experimental settings, the inhibition or knockout of TSLP signaling has shown great therapeutic potential. This, in conjunction with the increasing knowledge about the central role of TSLP in the pathogenesis of atopic diseases, has sparked an interest in TSLP as a druggable target. In this review, we will discuss the autocrine and paracrine effects of TSLP, how it regulates the tissue microenvironment and drives atopic diseases, which provide the rationale for the increasing interest in TSLP as a druggable target.

Keywords: Anti-inflammatory drugs; Atopic diseases; Atopic march; TSLP; Th2 inflammation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Biological Products / pharmacology
  • Cellular Microenvironment / physiology
  • Cytokines / drug effects*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Progression
  • Humans
  • Hypersensitivity / physiopathology*
  • Inflammation Mediators / physiology
  • Janus Kinases / metabolism
  • Protein Isoforms
  • Severity of Illness Index
  • Signal Transduction / physiology
  • Th2 Cells / metabolism
  • Thymic Stromal Lymphopoietin

Substances

  • Biological Products
  • Cytokines
  • Inflammation Mediators
  • Protein Isoforms
  • Janus Kinases
  • Thymic Stromal Lymphopoietin