New developments implicating IL-21 in autoimmune disease

J Autoimmun. 2021 Aug:122:102689. doi: 10.1016/j.jaut.2021.102689. Epub 2021 Jul 2.

Abstract

Elevated interleukin (IL)-21 is a common finding in the tissues and/or sera of patients with autoimmune disease. CD4 T cells are the primary producers of IL-21; often the IL-21 producing CD4 T cells will express molecules associated with follicular helper cells (TFH). Recent work has shown that the CD4 T cell-derived IL-21 is able to promote effector functions and memory differentiation of CD8 T cells in chronic infections and cancer. Autoimmunity has similarities to chronic infections and cancer. However, CD4 T cell-derived IL-21:IL21R signaling in CD8 T cells has not been fully appreciated in the context of autoimmunity. In this review, we assess the current knowledge regarding CD4 T cell-derived IL-21 and IL21R signaling within CD8 T cells and evaluate what implications it has within several autoimmune diseases including systemic lupus erythematous, rheumatoid arthritis, juvenile idiopathic arthritis, type 1 diabetes mellitus, psoriasis, Sjögren's syndrome, vitiligo, antiphospholipid syndrome, pemphigus, and giant cell arteritis.

Keywords: Autoimmunity; CD4 T cells; CD8 T cells; Interleukin (IL)-21; Resident memory.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Disease Models, Animal
  • Humans
  • Immunologic Memory
  • Interleukins / metabolism*
  • Receptors, Interleukin-21 / metabolism
  • Signal Transduction / immunology
  • T Follicular Helper Cells / immunology*
  • T Follicular Helper Cells / metabolism

Substances

  • Interleukins
  • Receptors, Interleukin-21
  • interleukin-21