Format

Send to

Choose Destination
J Autoimmun. 2019 May 9. pii: S0896-8411(18)30668-1. doi: 10.1016/j.jaut.2019.04.017. [Epub ahead of print]

Interleukin 22 ameliorates neuropathology and protects from central nervous system autoimmunity.

Author information

1
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
2
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, 20892, USA. Electronic address: caspir@nei.nih.gov.

Abstract

IL-22 has opposing effects in different tissues, from pro-inflammatory (skin, joints) to protective (liver, intestine) but little is known about its effects on neuroinflammation. We examined the effect of IL-22 on retinal tissue by using the model of experimental autoimmune uveitis (EAU) in IL-22-/- mice, as well as by intraocular injections of recombinant IL-22 or anti-IL-22 antibodies in wild type animals. During EAU, IL-22 was produced in the eye by CD4+ eye-infiltrating T cells. EAU-challenged IL-22-/- mice, as well as WT mice treated systemically or intraocularly with anti-IL-22 antibodies during the expression phase of disease, developed exacerbated retinal damage. Furthermore, IL-22-/- mice were more susceptible than WT controls to glutamate-induced neurotoxicity, whereas local IL-22 supplementation was protective, suggesting direct or indirect neuroprotective effects. Mechanistic studies revealed that retinal glial Müller cells express IL-22rα1 in vivo, and in vitro IL-22 enhanced their ability to suppress proliferation of effector T cells. Finally, IL-22 injected into the eye concurrently with IL-1, inhibited the (IL-1-induced) expression of multiple proinflammatory and proapoptotic genes in retinal tissue. These findings suggest that IL-22 can function locally within the retina to reduce inflammatory damage and provide neuroprotection by affecting multiple molecular and cellular pathways.

KEYWORDS:

Autoimmune; IL-22; IRBP; Neuroprotection; Uveitis

PMID:
31080013
DOI:
10.1016/j.jaut.2019.04.017

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center