| First Author | Mattapallil MJ | Year | 2019 |
| Journal | J Autoimmun | Volume | 102 |
| Pages | 65-76 | PubMed ID | 31080013 |
| Mgi Jnum | J:294410 | Mgi Id | MGI:6456313 |
| Doi | 10.1016/j.jaut.2019.04.017 | Citation | Mattapallil MJ, et al. (2019) Interleukin 22 ameliorates neuropathology and protects from central nervous system autoimmunity. J Autoimmun 102:65-76 |
| abstractText | 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 Muller cells express IL-22ralpha1 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. |
