MHC class II expression and potential antigen-presenting cells in the retina during experimental autoimmune uveitis
| Autor: | Deborah A. Lipski, Vincent Foucart, Francois Willermain, Remi Dewispelaere, Catherine Bruyns, Matthieu Defrance, Laure Caspers |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Adoptive cell transfer Blood-retinal barrier T cell Immunology Antigen presentation Genes MHC Class II Antigen-Presenting Cells Gene Expression Major histocompatibility complex lcsh:RC346-429 Retina Autoimmune Diseases Uveitis 03 medical and health sciences Cellular and Molecular Neuroscience Mice Neurologie MHC class I Immunologie medicine Animals Humans RNA-Seq Amino Acid Sequence Antigen-presenting cell lcsh:Neurology. Diseases of the nervous system Inflammation MHC class II biology Microglia General Neuroscience Research Macrophages Autoimmune eye disorders Cell biology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Neurology Ly6C biology.protein Co-stimulatory molecules Transcriptome Sciences cognitives |
| Zdroj: | Journal of Neuroinflammation Journal of neuroinflammation, 14 (1 Journal of Neuroinflammation, Vol 14, Iss 1, Pp 1-22 (2017) |
| ISSN: | 1742-2094 |
| Popis: | Background: Controversy exists regarding which cell types are responsible for autoantigen presentation in the retina during experimental autoimmune uveitis (EAU) development. In this study, we aimed to identify and characterize the retinal resident and infiltrating cells susceptible to express major histocompatibility complex (MHC) class II during EAU. Methods: EAU was induced in C57BL/6 mice by adoptive transfer of autoreactive lymphocytes from IRBP1-20-immunized animals. MHC class II expression was studied by immunostainings on eye cryosections. For flow cytometry (FC) analysis, retinas were dissected and enzymatically digested into single-cell suspensions. Three MHC class II+ retinal cell populations were sorted by FC, and their RNA processed for RNA-Seq. Results: Immunostainings demonstrate strong induction of MHC class II expression in EAU, especially in the inner retina at the level of inflamed vessels, extending to the outer retinal layers and the subretinal space in severely inflamed eyes. Most MHC class II+ cells express the hematopoietic marker IBA1. FC quantitative analyses demonstrate that MHC class II induction significantly correlates with disease severity and is associated with upregulation of co-stimulatory molecule expression. In particular, most MHC class IIhi cells express co-stimulatory molecules during EAU. Further phenotyping identified three MHC class II+ retinal cell populations: CD45-CD11b- non-hematopoietic cells with low MHC class II expression and CD45+CD11b+ hematopoietic cells with higher MHC class II expression, which can be further separated into Ly6C+ and Ly6C- cells, possibly corresponding to infiltrating macrophages and resident microglia. Transcriptome analysis of the three sorted populations leads to a clear sample clustering with some enrichment in macrophage markers and microglial cell markers in Ly6C+ and Ly6C- cells, respectively. Functional annotation analysis reveals that both hematopoietic cell populations are more competent in MHC class II-associated antigen presentation and in T cell activation than non-hematopoietic cells. Conclusion: Our results highlight the potential of cells of hematopoietic origin in local antigen presentation, whatever their Ly6C expression. Our work further provides a first transcriptomic study of MHC class II-expressing retinal cells during EAU and delivers a series of new candidate genes possibly implicated in the pathogenesis of retinal autoimmunity. SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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