{"doi":"10.1016/j.ebiom.2021.103516","title":"Tailoring immune cell behavior to stop autoimmune disease","abstract":"While the ocular microenvironment normally expresses within its tissue microenvironment potent suppressors of inflammation, it is still susceptible, albeit rare, to autoimmune disease. Uveitis is a general term for intraocular inflammation that includes idiopathic inflammation assumed to be autoimmune in nature. The incidence rate of uveitis is 17–115 cases per 100,000 persons [[1]Gritz DC Wong IG. Incidence and prevalence of uveitis in Northern California; the Northern California Epidemiology of Uveitis Study.Ophthalmology. 2004; 111 (discussion PubMed PMID: 15019324): 491-500Summary Full Text Full Text PDF PubMed Scopus (573) Google Scholar,[2]Wakefield D Chang JH. Epidemiology of uveitis.Int Ophthalmol Clin. 2005; 45 (PubMed PMID: 15791154): 1-13Crossref PubMed Scopus (154) Google Scholar]. This makes it the third leading cause of blindness in the United States, and the standard therapy, like for most inflammatory diseases, is corticosteroids. This treatment is effective for many; however, as much as 60% of treated patients will have a recurrence of uveitis within 5 years and almost 18% of the patients become unresponsive to corticosteroid treatment to suffer chronic uveitis [[3]Teoh SC Dick AD. Diagnostic techniques for inflammatory eye disease: past, present and future: a review.BMC ophthalmology. 2013; 13 (PubMed PMID: 23926885. PMCID: PMC3750647. Epub 2013/08/10): 41Crossref PubMed Scopus (5) Google Scholar]. Therapeutic alternatives like biologics rely mostly on a trial-and-error approach to find an effective dose that balances between suppressing uveitis and susceptibility to infections and side effects [[4]Pasadhika S Rosenbaum JT. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis.Biologics. 2014; 8 (PubMed PMID: 24600203. PMCID: PMC3933243): 67-81PubMed Google Scholar]. Each time an attempt fails vision is further degraded by the uveitis. Therefore, therapies that focus on the autoimmune activity targeting the eye with minimal side-effects would improve the health and quality of life for patients with chronic uveitis. The most common used animal model for uveitis is Experimental Autoimmune Uveitis (EAU) in mice. Many research groups have used EAU to not only understand the immunobiology of uveitis, but also evaluate the effects of therapeutic approaches to suppress uveitis. This model differs from human uveitis in that it is not spontaneous. Also, it resolves without intervention; however, there is substantial damage to the retina. This self-resolution of EAU is mediated by emergence of Treg cells with retinal-antigen specificity [[5]Silver PB Horai R Chen J Jittayasothorn Y Chan CC Villasmil R et al.Retina-specific T regulatory cells bring about resolution and maintain remission of autoimmune uveitis.J Immunol. 2015; 194 (PubMed PMID: 25716996. PMCID: PMC4459505. Epub 2015/02/27): 3011-3019Crossref PubMed Scopus (51) Google Scholar,[6]Lee DJ Taylor AW. Both MC5r and A2Ar are required for protective regulatory immunity in the spleen of post-experimental autoimmune uveitis in mice.J Immunol. 2013; 191 (PubMed PMID: 24043903. PMCID: PMC3796047. Epub 2013/09/18): 4103-4111Crossref PubMed Scopus (41) Google Scholar]. This has suggested that an approach that can augment Treg cell activity during uveitis can promote resolution, provide long term resistance to recurrence, and hopefully preserve vision. In the manuscript by Chen et al. [[7]Chen Z. Zhang T. Kam H. et al.Induction of antigen-specific Treg cells in treating autoimmune uveitis via bystander suppressive pathways without compromising anti-tumor immunity.EBioMedicine. 2021; 70103496Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar] they demonstrated an approach to expanding retinal-antigen specific Treg cells during EAU using anti-CD4-antibody (αCD4 Ab) therapy along with injecting retinal antigens. This generated antigen-specific Treg cells that suppress EAU. The approach to use αCD4 Ab is based on the idea tha","journal":"EBioMedicine","year":2021,"id":226099,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9621,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":652935,"name":"Andrew W. Taylor","orcid":"0000-0002-0330-8591","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","pmid":"34364167","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":[]}