TSLP acts on regulatory T cells to maintain their identity and limit allergic inflammation

Sci Immunol. 2025 Jan 10;10(103):eadk0073. doi: 10.1126/sciimmunol.adk0073. Epub 2025 Jan 10.

Abstract

Thymic stromal lymphopoietin (TSLP) is a type I cytokine that promotes allergic responses and mediates type 2 immunity. A balance between effector T cells (Teffs), which drive the immune response, and regulatory T cells (Tregs), which suppress the response, is required for proper immune homeostasis. Here, we report that TSLP differentially acts on Teffs versus Tregs to balance type 2 immunity. As expected, deletion of TSLP receptor (TSLPR) on all T cells (Cd4CreCrlf2fl/fl mice) resulted in lower numbers of T helper 2 (TH2) cells and diminished ovalbumin-induced airway inflammation, but selective deletion of TSLPR on Tregs (Foxp3YFP-Cre/YCrlf2fl/fl mice) resulted in increased interleukin-5 (IL-5)- and IL-13-secreting TH2 cells and lung eosinophilia. Moreover, TSLP augmented the expression of factors that stabilize Tregs. During type 2 immune responses, TSLPR-deficient Tregs acquired TH2-like properties, with augmented GATA3 expression and secretion of IL-13. TSLP not only is a driver of TH2 effector cells but also acts in a negative feedback loop, thus promoting the ability of Tregs to limit allergic inflammation.

MeSH terms

  • Animals
  • Cytokines* / immunology
  • Cytokines* / metabolism
  • Hypersensitivity / immunology
  • Immunoglobulins
  • Inflammation / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / immunology
  • T-Lymphocytes, Regulatory* / immunology
  • Th2 Cells / immunology
  • Thymic Stromal Lymphopoietin*

Substances

  • Cytokines
  • Thymic Stromal Lymphopoietin
  • TSLP protein, mouse
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • Immunoglobulins