Abstract
BackgroundIncreasing evidences link T helper 17 (Th17) cells with multiple sclerosis (MS). In this context, interleukin-22 (IL-22), a Th17-linked cytokine, has been implicated in blood brain barrier breakdown and lymphocyte infiltration. Furthermore, polymorphism between MS patients and controls has been recently described in the gene coding for IL-22 binding protein (IL-22BP). Here, we aimed to better characterize IL-22 in the context of MS.MethodsIL-22 and IL-22BP expressions were assessed by ELISA and qPCR in the following compartments of MS patients and control subjects: (1) the serum, (2) the cerebrospinal fluid, and (3) immune cells of peripheral blood. Identification of the IL-22 receptor subunit, IL-22R1, was performed by immunohistochemistry and immunofluorescence in human brain tissues and human primary astrocytes. The role of IL-22 on human primary astrocytes was evaluated using 7-AAD and annexin V, markers of cell viability and apoptosis, respectively.ResultsIn a cohort of 141 MS patients and healthy control (HC) subjects, we found that serum levels of IL-22 were significantly higher in relapsing MS patients than in HC but also remitting and progressive MS patients. Monocytes and monocyte-derived dendritic cells contained an enhanced expression of mRNA coding for IL-22BP as compared to HC.Using immunohistochemistry and confocal microscopy, we found that IL-22 and its receptor were detected on astrocytes of brain tissues from both control subjects and MS patients, although in the latter, the expression was higher around blood vessels and in MS plaques.Cytometry-based functional assays revealed that addition of IL-22 improved the survival of human primary astrocytes. Furthermore, tumor necrosis factor α-treated astrocytes had a better long-term survival capacity upon IL-22 co-treatment. This protective effect of IL-22 seemed to be conferred, at least partially, by a decreased apoptosis.ConclusionsWe show that (1) there is a dysregulation in the expression of IL-22 and its antagonist, IL-22BP, in MS patients, (2) IL-22 targets specifically astrocytes in the human brain, and (3) this cytokine confers an increased survival of the latter cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0335-3) contains supplementary material, which is available to authorized users.
Highlights
Increasing evidences link T helper 17 (Th17) cells with multiple sclerosis (MS)
We found that the supernatant of SEB-stimulated Peripheral blood mononuclear cells (PBMC) of 74 MS patients secreted a higher amount of IL-22 than of 32 healthy control (HC) (p = 0.0436, Fig. 1d), a finding which was ascribable to the active category of MS patients
We found that CD4+ T cells accounted for most of the production of IL-22; and as already reported, monocytes, B cells, CD8+ T cells, and natural killer (NK) cells were able to produce and secrete significant amount of IL-22 (Additional file 1: Figure S1) [40]
Summary
Increasing evidences link T helper 17 (Th17) cells with multiple sclerosis (MS) In this context, interleukin-22 (IL-22), a Th17-linked cytokine, has been implicated in blood brain barrier breakdown and lymphocyte infiltration. Further suggesting that IL-22 may be involved in MS, genetic studies showed that the gene coding for IL-22 binding protein (IL-22BP, called IL-22RA2), an antagonist of IL-22 [27,28,29,30], harbored different single nucleotide polymorphism in MS patients as compared to control subjects [31,32,33,34] This secreted IL22 inhibitory receptor exacerbates experimental autoimmune encephalomyelitis (EAE) disease course [31, 35], raising the question whether IL-22 itself may have an antiinflammatory function in EAE
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
