Transient Upregulation of Indoleamine 2,3-Dioxygenase in Dendritic Cells by Human Chorionic Gonadotropin Downregulates Autoimmune Diabetes

• DOI: 10.2337/db06-1727
• Publication Date: 2007-05-26T03:53:57Z
• Authors: Aito Ueno; Suzanne Cho; Lu Cheng; Jianxiong Wang; Sheng Hou; Hiroko Nakano; Pere Santamaria; Yang Yang
• Keywords: Indoleamine 2,3-dioxygenase; Human chorionic gonadotropin; Gonadotropin

Pregnancy induces a state of immunological tolerance that aims at suppressing immune responses against the fetus and has been linked to temporal remission preexisting autoimmune disorders. To understand mechanisms this reversible regulation, we investigated role key pregnancy hormone, human chorionic gonadotropin (hCG), in type 1 diabetes nonobese diabetic (NOD) mice.We injected hCG into cytokine gene-deficient NOD mice evaluated effects administration on T-cells dendritic cells (DCs).We show inhibits both activation diabetogenic CD4(+) CD8(+) T-cells, vitro vivo, progression by upregulating expression indoleamine 2,3-dioxygenase (IDO) DCs. IDO upregulation is transient declined shortly after withdrawal. DC depletion restores diabetetogenic activity splenic from hCG-treated mice, inhibition 1-methyl-tryptophan abrogates hCG-induced T-cell suppression resistance diabetes.We propose DCs plays major pregnancy-associated autoimmunity.