T1/ST2 is preferentially expressed on murine Th2 cells, independent of interleukin 4, interleukin 5, and interleukin 10, and important for Th2 effector function

TLDR

T helper cells are classified by cytokine profiles, and the transient nature of cytokine expression creates a need for stable surface markers to distinguish Th1 and Th2 subsets that regulate immune responses. Identifying such stable markers could enable selective analysis and therapeutic modulation of Th subsets for allergic or autoimmune disease treatment. The study screened for genes preferentially expressed in Th2 cells (IL‑4, IL‑5, IL‑10 producers) but not in Th1 cells, uncovering candidate surface markers. T1/ST2 is stably expressed on Th2 cells independently of IL‑4/5/10, is essential for Th2 effector function, and its blockade or supplementation reduces airway eosinophilic inflammation and IL‑4/5 production in vivo.

Abstract

T helper (Th) cells can be categorized according to their cytokine expression. The differential induction of Th cells expressing Th1 and/or Th2 cytokines is key to the regulation of both protective and pathological immune responses. Cytokines are expressed transiently and there is a lack of stably expressed surface molecules, significant for functionally different types of Th cells. Such molecules are of utmost importance for the analysis and selective functional modulation of Th subsets and will provide new therapeutic strategies for the treatment of allergic or autoimmune diseases. To this end, we have identified potential target genes preferentially expressed in Th2 cells, expressing interleukin (IL)-4, IL-5, and/or IL-10, but not interferon-γ. One such gene, T1/ST2, is expressed stably on both Th2 clones and Th2-polarized cells activated in vivo or in vitro . T1/ST2 expression is independent of induction by IL-4, IL-5, or IL-10. T1/ST2 plays a critical role in Th2 effector function. Administration of either a mAb against T1/ST2 or recombinant T1/ST2 fusion protein attenuates eosinophilic inflammation of the airways and suppresses IL-4 and IL-5 production in vivo following adoptive transfer of Th2 cells.