Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis
Abstract Autoimmune uveitis (AU) is a kind of immune‐mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to disease initiation and progression of AU remains unclear. Here, we induced an...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-04-01
|
| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.534 |
| _version_ | 1797206941294919680 |
|---|---|
| author | Jiangyi Liu Xingyun Liao Na Li Zongren Xu Wang Yang Hongxiu Zhou Yusen Liu Zhi Zhang Guoqing Wang Shengping Hou |
| author_facet | Jiangyi Liu Xingyun Liao Na Li Zongren Xu Wang Yang Hongxiu Zhou Yusen Liu Zhi Zhang Guoqing Wang Shengping Hou |
| author_sort | Jiangyi Liu |
| collection | DOAJ |
| description | Abstract Autoimmune uveitis (AU) is a kind of immune‐mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to disease initiation and progression of AU remains unclear. Here, we induced an experimental AU (EAU) model with IRBP651‐670 and found that day[D]14 was the inflammatory summit with remarking clinical and histopathological manifestations and the activation of retinal microglia exhibited a time‐dependent pattern in the EAU course. We conducted single‐cell RNA sequencing of retinal immune cells in EAU mice at four time points and found microglia constituting the largest proportion, especially on D14. A novel inflammatory subtype (Cd74high Ccl5high) of retinal microglia was identified at the disease peak that was closely associated with modulating immune responses. In vitro experiments indicated that inflammatory stimuli induced proinflammatory microglia with the upregulation of CD74 and CCL5, and CD74 overexpression in microglia elicited their proinflammatory phenotype via nuclear factor‐kappa B signaling that could be attenuated by the treatment of neutralizing CCL5 antibody to a certain extent. In‐vivo blockade of Cd74 and Ccl5 effectively alleviated retinal microglial activation and disease phenotype of EAU. Therefore, we propose targeting CD74 and CCL5 of retinal microglia as promising strategies for AU treatment. |
| first_indexed | 2024-04-24T09:15:01Z |
| format | Article |
| id | doaj.art-950c88ce32a247dba87b0802384468f3 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-04-24T09:15:01Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-950c88ce32a247dba87b0802384468f32024-04-15T17:04:29ZengWileyMedComm2688-26632024-04-0154n/an/a10.1002/mco2.534Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitisJiangyi Liu0Xingyun Liao1Na Li2Zongren Xu3Wang Yang4Hongxiu Zhou5Yusen Liu6Zhi Zhang7Guoqing Wang8Shengping Hou9The First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaDepartment of Laboratory Medicine Beijing Tongren Hospital Capital Medical University Beijing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaDepartment of Kidney First Affiliated Hospital Third Military Medical University (Army Medical University) Chongqing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaThe First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory for the Prevention and Treatment of Major Blinding Eye Diseases Chongqing Eye Institute Chongqing ChinaAbstract Autoimmune uveitis (AU) is a kind of immune‐mediated disease resulting in irreversible ocular damage and even permanent vision loss. However, the precise mechanism underlying dynamic immune changes contributing to disease initiation and progression of AU remains unclear. Here, we induced an experimental AU (EAU) model with IRBP651‐670 and found that day[D]14 was the inflammatory summit with remarking clinical and histopathological manifestations and the activation of retinal microglia exhibited a time‐dependent pattern in the EAU course. We conducted single‐cell RNA sequencing of retinal immune cells in EAU mice at four time points and found microglia constituting the largest proportion, especially on D14. A novel inflammatory subtype (Cd74high Ccl5high) of retinal microglia was identified at the disease peak that was closely associated with modulating immune responses. In vitro experiments indicated that inflammatory stimuli induced proinflammatory microglia with the upregulation of CD74 and CCL5, and CD74 overexpression in microglia elicited their proinflammatory phenotype via nuclear factor‐kappa B signaling that could be attenuated by the treatment of neutralizing CCL5 antibody to a certain extent. In‐vivo blockade of Cd74 and Ccl5 effectively alleviated retinal microglial activation and disease phenotype of EAU. Therefore, we propose targeting CD74 and CCL5 of retinal microglia as promising strategies for AU treatment.https://doi.org/10.1002/mco2.534autoimmune uveitisCcl5Cd74microgliasingle‐cell RNA sequencing |
| spellingShingle | Jiangyi Liu Xingyun Liao Na Li Zongren Xu Wang Yang Hongxiu Zhou Yusen Liu Zhi Zhang Guoqing Wang Shengping Hou Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis MedComm autoimmune uveitis Ccl5 Cd74 microglia single‐cell RNA sequencing |
| title | Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis |
| title_full | Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis |
| title_fullStr | Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis |
| title_full_unstemmed | Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis |
| title_short | Single‐cell RNA sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis |
| title_sort | single cell rna sequencing reveals inflammatory retinal microglia in experimental autoimmune uveitis |
| topic | autoimmune uveitis Ccl5 Cd74 microglia single‐cell RNA sequencing |
| url | https://doi.org/10.1002/mco2.534 |
| work_keys_str_mv | AT jiangyiliu singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT xingyunliao singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT nali singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT zongrenxu singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT wangyang singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT hongxiuzhou singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT yusenliu singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT zhizhang singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT guoqingwang singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis AT shengpinghou singlecellrnasequencingrevealsinflammatoryretinalmicrogliainexperimentalautoimmuneuveitis |