Abstract: Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.

Abstract: A composition and method for treating autoimmune disease includes administering an effective amount of an aryl hydrocarbon receptor (AhR) ligand. The AhR ligand includes 11-Cl-BBQ, 10-Cl-BBQ, an analog of 11-Cl-BBQ, or combination thereof. The AhR ligand is administered topically, orally, transdermally, intravenously, subcutaneously, or with a nanoparticle. The AhR ligand induces regulatory T cells (AhR-Tregs). AhR-Treg cells block the differentiation of cytotoxic T-lymphocytes (CTL). The AhR ligand activates AhR in CD4+ T cells to induce CD4+ AhR-Tregs that suppress the development of effector CTL, thereby suppressing the development of CTL that attack host cells in graft versus host disease (GVHD) or ?-cells in the pancreas in diabetes mellitus type 1 (T1DM). The AhR ligand can also suppress development of CTL independently of Foxp3+ regulatory T cell induction. The AhR ligand can therefore be used to treat autoimmune diseases characterized by an absence of functional Foxp3+ regulatory T cell.

Abstract: A composition and method for treating autoimmune disease includes administering an effective amount of an aryl hydrocarbon receptor (AhR) ligand. The AhR ligand includes 11-Cl-BBQ, 10-Cl-BBQ, an analog of 11-Cl-BBQ, or combination thereof. The AhR ligand is administered topically, orally, transdermally, intravenously, subcutaneously, or with a nanoparticle. The AhR ligand induces regulatory T cells (AhR-Tregs). AhR-Treg cells block the differentiation of cytotoxic T-lymphocytes (CTL). The AhR ligand activates AhR in CD4+ T cells to induce CD4+ AhR-Tregs that suppress the development of effector CTL, thereby suppressing the development of CTL that attack host cells in graft versus host disease (GVHD) or ?-cells in the pancreas in diabetes mellitus type 1 (T1DM). The AhR ligand can also suppress development of CTL independently of Foxp3+ regulatory T cell induction. The AhR ligand can therefore be used to treat autoimmune diseases characterized by an absence of functional Foxp3+ regulatory T cell.