Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.

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Tytuł:: Therapeutic Effect of IL-38 on Experimental Autoimmune Uveitis: Reprogrammed Immune Cell Landscape and Reduced Th17 Cell Pathogenicity.
Autorzy:: Li H; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Zhu L; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Wang R; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Xie L; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Chen Y; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Duan R; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Liu X; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Huang Z; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Chen B; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Li Z; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Wang X; Eye Center of Xiangya Hospital, Central South University, Changsha, China.; Hunan Key Laboratory of Ophthalmology, Xiangya Hospital, Central South University, Changsha, China.
Su W; State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.
Źródło:: Investigative ophthalmology & visual science [Invest Ophthalmol Vis Sci] 2021 Dec 01; Vol. 62 (15), pp. 31.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: Brookline Ma : Association For Research In Vision And Ophthalmology (Arvo)
Original Publication: St. Louis, Mosby.
MeSH Terms:: Autoimmune Diseases/*drug therapy
Immune System/*physiology
Interleukins/*therapeutic use
Th17 Cells/*immunology
Uveitis/*drug therapy
Adoptive Transfer ; Animals ; Antigen-Presenting Cells/immunology ; Autoimmune Diseases/chemically induced ; Autoimmune Diseases/immunology ; B-Lymphocytes/immunology ; Coculture Techniques ; Disease Models, Animal ; Enzyme-Linked Immunosorbent Assay ; Female ; Flow Cytometry ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Injections, Intravenous ; Interleukin-23/metabolism ; Lymph Nodes/immunology ; Mice ; Mice, Inbred C57BL ; Neck ; Recombinant Proteins/therapeutic use ; Retina/immunology ; Sequence Analysis, RNA ; Single-Cell Analysis ; T-Lymphocytes/immunology ; Th1 Cells/immunology ; Uveitis/chemically induced ; Uveitis/immunology
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Substance Nomenclature:: 0 (Interleukin-23)
0 (Interleukins)
0 (Recombinant Proteins)
83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
Entry Date(s):: Date Created: 20211230 Date Completed: 20220114 Latest Revision: 20231105
Update Code:: 20240104
PubMed Central ID:: PMC8727319
DOI:: 10.1167/iovs.62.15.31
PMID:: 34967854
: Czasopismo naukowe

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Purpose: The purpose of this study was to elucidate the effects of interleukin (IL)-38 on experimental autoimmune uveitis (EAU) and its underlying mechanisms.
Methods: Mice with EAU were treated with IL-38, and the retinas and cervical draining lymph nodes (CDLNs) were analyzed by flow cytometry. Single-cell RNA sequencing (scRNA-seq) was conducted to analyze the immune cell profiles of CDLNs from normal, EAU, and IL-38-treated mice.
Results: Administration of IL-38 attenuated EAU symptoms and reduced the proportion of T helper 17 (Th17) and T helper 1 (Th1) cells in the retinas and CDLNs. In scRNA-seq analysis, IL-38 downregulated the IL-17 signaling pathway and reduced the expression of Th17 cell pathogenicity-related genes (Csf2 and Il23r), findings which were also confirmed by flow cytometry. In vitro, IL-38 reduced the granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation function of IL-23 and inhibited IL-23R expression in Th17 cells. Moreover, when co-cultured with Th17 cells, IL-38 prevented IL-23 production in antigen-presenting cells (APCs).
Conclusions: Our data demonstrate the therapeutic effect of IL-38 on EAU, and suggest that the effect of IL-38 may be caused by dampening of the GM-CSF/IL-23R/IL-23 feedback loop between Th17 cells and APCs.

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