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Transient upregulation of IDO in dendritic cells by human chorionic gonadotropin downregulates autoimmune diabetes

¹Julia McFarlane Diabetes Research Centre, Department of Biochemistry and Molecular Biology
²Department of Microbiology and Infectious Diseases, Faculty of Medicine, The University of Calgary, Canada

Correspondence: yyang{at}ucalgary.ca

Objective:: Pregnancy induces a state of immunological tolerance that aims at suppressing immune responses against the fetus and has been linked to temporal remission of pre-existing autoimmune disorders. To understand the mechanisms of this reversible immune regulation, we investigate the role of a key pregnancy hormone, human chorionic gonadotropin (hCG), in immune tolerance against autoimmune type 1 diabetes in nonobese diabetic (NOD) mice.

Research Design and methods:: We injected hCG into cytokine gene deficient NOD mice, and evaluated the effects of hCG administration on T cells and dendritic cells (DCs).

Results and conclusions:: We show that administration of hCG to NOD mice inhibits both the activation of diabetogenic CD4⁺ and CD8⁺ T cells, in vitro and in vivo, and the progression of T1D by upregulating the expression of indoleamine 2,3-dioxygenase (IDO) in dendritic cells (DCs). IDO upregulation is transient and declined shortly after hCG withdrawal. DC-depletion restores the diabetetogenic activity of splenic T cells from hCG-treated mice, and inhibition of IDO activity by 1-methyl-tryptophan (1-MT) abrogates the hCG-induced T cell suppression and resistance to T1D. We propose that hCG-induced upregulation of IDO in DCs plays a major role in pregnancy-associated resistance to autoimmunity.

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