The Kynurenine Pathway-New Linkage between Innate and Adaptive Immunity in Autoimmune Endocrinopathies

Int J Mol Sci. 2021 Sep 13;22(18):9879. doi: 10.3390/ijms22189879.

Abstract

The kynurenine pathway (KP) is highly regulated in the immune system, where it promotes immunosuppression in response to infection or inflammation. Indoleamine 2,3-dioxygenase 1 (IDO1), the main enzyme of KP, has a broad spectrum of activity on immune cells regulation, controlling the balance between stimulation and suppression of the immune system at sites of local inflammation, relevant to a wide range of autoimmune and inflammatory diseases. Various autoimmune diseases, among them endocrinopathies, have been identified to date, but despite significant progress in their diagnosis and treatment, they are still associated with significant complications, morbidity, and mortality. The precise cellular and molecular mechanisms leading to the onset and development of autoimmune disease remain poorly clarified so far. In breaking of tolerance, the cells of the innate immunity provide a decisive microenvironment that regulates immune cells' differentiation, leading to activation of adaptive immunity. The current review provided a comprehensive presentation of the known role of IDO1 and KP activation in the regulation of the innate and adaptive arms of the immune system. Significant attention has been paid to the immunoregulatory role of IDO1 in the most prevalent, organ-specific autoimmune endocrinopathies-type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis.

Keywords: adaptive immunity; autoimmune disease; autoimmune endocrinopathies; autoimmune thyroiditis; indoleamine 2,3-dioxygenase 1 (IDO1); innate immunity; kynurenine pathway (KP); type 1 diabetes mellitus (T1DM).

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / genetics*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology*
  • Endocrine System Diseases / genetics
  • Endocrine System Diseases / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Kynurenine / genetics*
  • Kynurenine / immunology
  • Kynurenine / metabolism
  • Signal Transduction / immunology

Substances

  • Kynurenine