Compounds and methods to suppress autoimmune response
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 β-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.
1. A method of treating an autoimmune disease treatable through induction of regulatory T-cells comprising administering a therapeutically effective amount of an aryl hydrocarbon receptor (AhR) ligand to a subject in need thereof, wherein the aryl hydrocarbon receptor (AhR) ligand is 11-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (11-Cl-BBQ), 7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one, 4,11-dichloro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one, 7-oxo-7H-benzimidazo[2,1-a]benzo[de]-isoquinoline-3-carboxylic acid, 11-trifluoro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one, or 10-chloro-7H-benzimidazo[2,1-a]benzo[de]isoquinolin-7-one.
2. The method of claim 1 , wherein the autoimmune disease is diabetes mellitus type 1.
3. The method of claim 1 , wherein the autoimmune disease is graft versus host disease.
4. The method of claim 1 , wherein the autoimmune disease is Celiac disease, autoimmune hepatitis, autoimmune pancreatitis, Crohn's disease, interstitial cystitis, microscopic colitis, or ulcerative colitis.
5. The method of claim 1 , wherein the autoimmune disease is alopecia areata, atopic dermatitis, cicatricial pemphigoid, dermatomyositis, dermatitis herpetiformis, lichen planus, pemphigus vulgaris, or psoriasis.
6. The method of claim 1 , wherein the aryl hydrocarbon receptor (AhR) ligand is administered topically.
7. The method of claim 1 , wherein the aryl hydrocarbon receptor (AhR) ligand is administered orally, transdermally, intravenously, subcutaneously, or with a nanoparticle.
8. The method of claim 1 , wherein the aryl hydrocarbon receptor (AhR) ligand is 11-chloro-7H-benzimidazo[2,1-a]benzo[de]Iso-quinolin-7-one (11-Cl-BBQ).
9. The method of claim 1 , further including administering the AhR ligand with a pharmaceutically acceptable carrier.