{"doi":"10.3389/fimmu.2024.1399989","title":"Retinal microglia express more MHC class I and promote greater T-cell-driven inflammation than brain microglia","abstract":"Introduction Macrophage function is determined by microenvironment and origin. Brain and retinal microglia are both derived from yolk sac progenitors, yet their microenvironments differ. Utilizing single-cell RNA sequencing (scRNA-seq) data from mice, we tested the hypothesis that retinal and brain microglia exhibit distinct transcriptional profiles due to their unique microenvironments. Methods Eyes and brains from 2-4 month wildtype mice were combined (20 eyes; 3 brains) to yield one biologically diverse sample per organ. Each tissue was digested into single cell suspensions, enriched for immune cells, and sorted for scRNA-seq. Analysis was performed in Seurat v3 including clustering, integration, and differential expression. Multi-parameter flow cytometry was used for validation of scRNA-seq results. Lymphocytic choriomeningitis virus (LCMV) Clone 13, which produces a systemic, chronic, and neurotropic infection, was used to validate scRNA-seq and flow cytometry results in vivo . Results Cluster analysis of integrated gene expression data from eye and brain identified 6 Tmem119 + P2ry12 + microglial clusters. Differential expression analysis revealed that eye microglia were enriched for more pro-inflammatory processes including antigen processing via MHC class I (14.0-fold, H2-D1 and H2-K1 ) and positive regulation of T-cell immunity (8.4-fold) compared to brain microglia. Multi-parameter flow cytometry confirmed that retinal microglia expressed 3.2-fold greater H2-Db and 263.3-fold more H2-Kb than brain microglia. On Day 13 and 29 after LCMV infection, CD8 + T-cell density was greater in the retina than the brain. Discussion Our data demonstrate that the microenvironment of retina and brain differs, resulting in microglia-specific gene expression changes. Specifically, retinal microglia express greater MHC class I by scRNA-seq and multi-parameter flow cytometry, resulting in a possibly enhanced capability to stimulate CD8 + T-cell inflammation during LCMV infection. These results may explain tissue-specific differences between retina and brain during systemic viral infections and CD8 + T-cell driven autoimmune disease.","journal":"Frontiers in Immunology","year":2024,"id":425993,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8967,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1224800,"name":"Joyce Gong","orcid":null,"position":1,"is_corresponding":false},{"id":457837,"name":"Steven Droho","orcid":null,"position":2,"is_corresponding":false},{"id":456348,"name":"Hadijat M. Makinde","orcid":"0000-0001-8492-4187","position":3,"is_corresponding":false},{"id":975938,"name":"Miranda G. Gurra","orcid":"0000-0002-1879-6575","position":4,"is_corresponding":false},{"id":1224801,"name":"Cecilia H. Stumpf","orcid":null,"position":5,"is_corresponding":false},{"id":875174,"name":"Arjun Kharel","orcid":"0000-0002-4203-5469","position":6,"is_corresponding":false},{"id":456351,"name":"Gaurav Gadhvi","orcid":"0000-0002-4379-2824","position":7,"is_corresponding":false},{"id":456349,"name":"Deborah R. Winter","orcid":"0000-0003-1806-673X","position":8,"is_corresponding":false},{"id":302507,"name":"Weiguo Cui","orcid":"0000-0003-1562-9218","position":9,"is_corresponding":false},{"id":456355,"name":"Carla M. Cuda","orcid":"0000-0002-2022-8171","position":10,"is_corresponding":false},{"id":456354,"name":"Jeremy A. Lavine","orcid":"0000-0002-0884-1336","position":11,"is_corresponding":false},{"id":456352,"name":"Christina L. Bloomfield","orcid":"0000-0002-6012-3745","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T01:58:32.160975Z","pmid":"38799448","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}