Comment and reply on:Emerging role of Th22 and IL-22 in multiple sclerosis, an autoimmune disease in the central nervous system

Dear Editors,

Tian and colleagues summarized the role of Th22 cells and IL-22 in inflammatory and autoimmune diseases [1]. Their review was well written, whereas it might be strengthened by supplementing some knowledge on the role of Th22 cells and IL-22 in multiple sclerosis (MS), an autoimmune disease in the nervous system.

MS is a chronic inflammatory demyelinating disorder of the central nervous system. Beyeen et al. established IL-22RA2 as a risk gene for MS through genetic investigation in a large-scale association study on a combined Swedish and Norwegian cohort comprising 5019 patients with MS [2]. They found that a single nucleotide polymorphism located at the end of IL-22RA2 associated with MS risk, displaying an odds ratio of 1.26 [2]. Given the fact that IL-22 and its receptors have been implicated in various chronic inflammations, their findings suggested that IL-22RA2 regulates a central immune pathway. A most recent study found that the proportion of Th22 cells and the level of IL-22 were increased in serum from patients with MS [3], indicating a role of Th22 cells and IL-22 in MS. This can further be confirmed in MS animal model experimental autoimmune encephalomyelitis (EAE) [2], which is a widely used tool to study neuroinflammatory disease mechanisms. In Beyeen et al.'s study, investigators performed high-resolution linkage analysis in a rat advanced intercross line to identify an EAE-regulating quantitative trait locus, Eae29, on rat chromosome 1 [2]. They found that Eae29 alleles from the resistant strain both conferred milder EAE and lower production of proinflammatory molecules in macrophages; the soluble IL-22R α2 gene lies within the Eae29 locus, and its expression was reduced, both in activated macrophages and splenocytes from immunized rats [2]. Furthermore, researchers in another group performed a detailed analysis of the dynamics of cytokine profile along the clinical course of EAE [4]. They found that levels of IL-22 were elevated during the induction and peak phases of EAE and were markedly decreased during the recovery phase [4]. Similarly, by studying genetic expression of several MS candidate genes in the myelin oligodendrocyte glycoprotein (MOG)-induced rat EAE model using susceptible DA and resistant PVG inbred strains, IL-22 was also found to be increased after the induction of EAE [5]. In summary, multiple lines of evidence have pointed to a role of Th22 cells and IL-22. The seeking for therapeutic strategies targeting them is warranted in future studies.

Declaration of interest

The authors state no conflict of interest and have received no payment in preparation of this manuscript.

Authors' response

Dear Editor,

We thank the authors for their thoughtful response to our study. They raise some knowledge on the role of Th22 cells and IL-22 in MS which we have not mentioned before in the review.

Autoimmune diseases are a group of disorders that occur when the immune system loses its ability to distinguish substances and tissues normally present in human body from exogenous antigens. These diseases include rheumatoid arthritis, inflammatory bowel diseases, psoriasis, atopic dermatitis, systemic lupus erythematosus, immune thrombocytopenia, ankylosing spondylitis, MS and so on. However, because of the limited space in our review, we did not demonstrate all the autoimmune diseases one by one and only described the roles of Th22 cells and IL-22 in autoimmune diseases that relatively frequently happened.

There have been some newly reported studies about the role of Th22 and IL-22 in MS since 2009. The authors reviewed them and wrote a Letter to the Editor in response to our article. We appreciate their comments.