Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis
IntroductionAutoimmune uveitis is a sight-threatening inflammatory eye disease driven by immune dysregulation. We previously introduced a therapeutic strategy involving the in vivo induction of retinal-antigen-specific regulatory T cells (Tregs) via αCD4 antibody injection followed by administration...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636901/full |
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| author | Dijie Qiao Lu Zhang Yajie Zhong Dongmei Liu Zilin Chen Wai Po Chong Wai Po Chong Wai Po Chong Jun Chen |
| author_facet | Dijie Qiao Lu Zhang Yajie Zhong Dongmei Liu Zilin Chen Wai Po Chong Wai Po Chong Wai Po Chong Jun Chen |
| author_sort | Dijie Qiao |
| collection | DOAJ |
| description | IntroductionAutoimmune uveitis is a sight-threatening inflammatory eye disease driven by immune dysregulation. We previously introduced a therapeutic strategy involving the in vivo induction of retinal-antigen-specific regulatory T cells (Tregs) via αCD4 antibody injection followed by administration of the retinal self-peptide IRBP1-20, which effectively suppresses inflammation during the onset of experimental autoimmune uveitis (EAU).MethodsWe evaluated the long-term therapeutic efficacy of this approach in a chronic EAU model. EAU was induced in C57BL/6 mice, and treatment was administered at each onset or relapse episode over a 28-week period. Disease progression was monitored by clinical scoring and funduscopy, with further assessment using histopathology and optical coherence tomography (OCT). Flow cytometry was employed to analyze immune cell infiltration, and RNA sequencing of ocular tissue was performed to assess gene expression changes.ResultsMice receiving aCD4 antibody and IRBP1-20 showed sustained disease control up to 28 weeks, with reduced ocular inflammation, less retinal damage on OCT, and decreased immune cell infiltration compared to untreated controls. Transcriptomic analysis revealed significant downregulation of inflammation-related genes following treatment.ConclusionThese findings support the long-term immunomodulatory effect of combining αCD4 antibody and retinal antigen injection, offering a potential strategy for managing chronic progressive autoimmune uveitis. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-c23ecc9b7e3e4b23a403a3bf5cf0f17f2025-08-22T05:26:54ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16369011636901Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitisDijie Qiao0Lu Zhang1Yajie Zhong2Dongmei Liu3Zilin Chen4Wai Po Chong5Wai Po Chong6Wai Po Chong7Jun Chen8State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaSchool of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, ChinaInstitute for Research and Continuing Education, Hong Kong Baptist University, Shenzhen, ChinaState Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, ChinaIntroductionAutoimmune uveitis is a sight-threatening inflammatory eye disease driven by immune dysregulation. We previously introduced a therapeutic strategy involving the in vivo induction of retinal-antigen-specific regulatory T cells (Tregs) via αCD4 antibody injection followed by administration of the retinal self-peptide IRBP1-20, which effectively suppresses inflammation during the onset of experimental autoimmune uveitis (EAU).MethodsWe evaluated the long-term therapeutic efficacy of this approach in a chronic EAU model. EAU was induced in C57BL/6 mice, and treatment was administered at each onset or relapse episode over a 28-week period. Disease progression was monitored by clinical scoring and funduscopy, with further assessment using histopathology and optical coherence tomography (OCT). Flow cytometry was employed to analyze immune cell infiltration, and RNA sequencing of ocular tissue was performed to assess gene expression changes.ResultsMice receiving aCD4 antibody and IRBP1-20 showed sustained disease control up to 28 weeks, with reduced ocular inflammation, less retinal damage on OCT, and decreased immune cell infiltration compared to untreated controls. Transcriptomic analysis revealed significant downregulation of inflammation-related genes following treatment.ConclusionThese findings support the long-term immunomodulatory effect of combining αCD4 antibody and retinal antigen injection, offering a potential strategy for managing chronic progressive autoimmune uveitis.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636901/fullautoimmune uveitisimmunotherapyregulatory T cells (Treg)long-term therapychronic inflammationanti-CD4 antibody |
| spellingShingle | Dijie Qiao Lu Zhang Yajie Zhong Dongmei Liu Zilin Chen Wai Po Chong Wai Po Chong Wai Po Chong Jun Chen Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis Frontiers in Immunology autoimmune uveitis immunotherapy regulatory T cells (Treg) long-term therapy chronic inflammation anti-CD4 antibody |
| title | Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis |
| title_full | Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis |
| title_fullStr | Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis |
| title_full_unstemmed | Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis |
| title_short | Combination of αCD4 antibody and retinal antigen injection induces long-term disease control in autoimmune uveitis |
| title_sort | combination of αcd4 antibody and retinal antigen injection induces long term disease control in autoimmune uveitis |
| topic | autoimmune uveitis immunotherapy regulatory T cells (Treg) long-term therapy chronic inflammation anti-CD4 antibody |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1636901/full |
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