Facile induction of immune tolerance by an interleukin-2-TGFβ surrogate agonist - PubMed
14 hours ago
- #immune tolerance
- #immunotherapy
- #Treg cells
- CD4+ regulatory T cells (Treg cells) are essential for immune tolerance.
- Peripherally induced Treg cells (pTreg cells) complement thymic Treg cells by broadening Treg cell reactivity.
- TGFβ and IL-2 synergistically promote functional pTreg cell development in vitro but their combined roles in vivo have not been fully exploited.
- An IL-2-TGFβ 'surrogate' co-agonist was designed using a single-chain fusion protein between IL-2 and a low-affinity TGFβ mimic agonist.
- The IL-2-TGFβ surrogate enables simultaneous cis-activation of IL-2-STAT5 and TGFβ-SMAD2/3 signalling in T cells expressing IL-2 receptors.
- The surrogate agonist robustly induced antigen-specific, functional, and stable pTreg cells in vivo in mice.
- Induced pTreg cells display an effector-like state with high RORγt expression, enabling efficient migration and suppression of intestinal inflammation.
- Treatment with the agonist effectively quelled immune activation in models of allergic inflammation and autoimmune neuroinflammation.
- The study suggests a strategy for inducing antigen-specific pTreg cells in vivo to establish immune tolerance in inflammatory, allergic, and autoimmune diseases.