Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity
Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt–Koyanagi–Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully und...
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| Veröffentlicht in: | Mucosal immunology 2022-02, Vol.15 (2), p.351-361 |
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| creator | Yamana, Satoshi Shibata, Kensuke Hasegawa, Eiichi Arima, Mitsuru Shimokawa, Shotaro Yawata, Nobuyo Takeda, Atsunobu Yamasaki, Sho Sonoda, Koh-Hei |
| description | Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt–Koyanagi–Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161
high
TRAV1-2
+
mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of
interleukin
(
Il
)
22
and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of
Il22
, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis. |
| doi_str_mv | 10.1038/s41385-021-00469-5 |
| format | Article |
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high
TRAV1-2
+
mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of
interleukin
(
Il
)
22
and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of
Il22
, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.</description><identifier>ISSN: 1933-0219</identifier><identifier>EISSN: 1935-3456</identifier><identifier>DOI: 10.1038/s41385-021-00469-5</identifier><identifier>PMID: 34775490</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Allergology ; Animals ; Antibodies ; Antigens ; Autoimmune diseases ; Autoimmunity ; Biomedical and Life Sciences ; Biomedicine ; Experimental autoimmune uveitis ; Experimental autoimmune uveoretinitis ; Eye - pathology ; Gastroenterology ; Humans ; Immunology ; Inflammation ; Interleukin 22 ; Lymphocytes T ; Metabolites ; Mice ; Mucosa ; Mucosal-Associated Invariant T Cells - metabolism ; Neuroprotection ; Pathology ; Retina ; Single-cell protein ; Uveitis ; Uveitis - metabolism ; Uveitis - pathology ; Uveomeningoencephalitic Syndrome ; Visual perception</subject><ispartof>Mucosal immunology, 2022-02, Vol.15 (2), p.351-361</ispartof><rights>The Author(s), under exclusive licence to Society for Mucosal Immunology 2021</rights><rights>2021. The Author(s), under exclusive licence to Society for Mucosal Immunology.</rights><rights>The Author(s), under exclusive licence to Society for Mucosal Immunology 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-54a8218996c418751815c79cc621b9ce818067f61076505e768d33e7e7e7dca03</citedby><cites>FETCH-LOGICAL-c503t-54a8218996c418751815c79cc621b9ce818067f61076505e768d33e7e7e7dca03</cites><orcidid>0000-0001-8794-7368</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34775490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamana, Satoshi</creatorcontrib><creatorcontrib>Shibata, Kensuke</creatorcontrib><creatorcontrib>Hasegawa, Eiichi</creatorcontrib><creatorcontrib>Arima, Mitsuru</creatorcontrib><creatorcontrib>Shimokawa, Shotaro</creatorcontrib><creatorcontrib>Yawata, Nobuyo</creatorcontrib><creatorcontrib>Takeda, Atsunobu</creatorcontrib><creatorcontrib>Yamasaki, Sho</creatorcontrib><creatorcontrib>Sonoda, Koh-Hei</creatorcontrib><title>Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity</title><title>Mucosal immunology</title><addtitle>Mucosal Immunol</addtitle><addtitle>Mucosal Immunol</addtitle><description>Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt–Koyanagi–Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161
high
TRAV1-2
+
mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of
interleukin
(
Il
)
22
and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of
Il22
, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.</description><subject>Allergology</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Autoimmune diseases</subject><subject>Autoimmunity</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Experimental autoimmune uveitis</subject><subject>Experimental autoimmune uveoretinitis</subject><subject>Eye - pathology</subject><subject>Gastroenterology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Inflammation</subject><subject>Interleukin 22</subject><subject>Lymphocytes T</subject><subject>Metabolites</subject><subject>Mice</subject><subject>Mucosa</subject><subject>Mucosal-Associated Invariant T Cells - metabolism</subject><subject>Neuroprotection</subject><subject>Pathology</subject><subject>Retina</subject><subject>Single-cell protein</subject><subject>Uveitis</subject><subject>Uveitis - metabolism</subject><subject>Uveitis - pathology</subject><subject>Uveomeningoencephalitic Syndrome</subject><subject>Visual perception</subject><issn>1933-0219</issn><issn>1935-3456</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kElPHDEQRq0oKDMsfyAHZIkLlw7ldns7ohFLpEFc4MTBKjweMOpuT7wg8e_TwxAi5RDVwSXVq8-lR8h3Bj8YcH2WO8a1aKBlDUAnTSO-kDkzXDS8E_Lre8-3YzMj-zm_AEgAwb-RGe-UEp2BOXm4qS5m7BvMObqAxa9oGF8xBRwLvaPO932mz_jqaXn2CTe-luDoJhY_loA9xScMYy40utpjolhLDMNQx1DeDsneGvvsjz7eA3J_eXG3uG6Wt1c_F-fLxgngpREd6pZpY6TrmFaCaSacMs7Jlj0a5zXTINVaMlBSgPBK6hXnXm1r5RD4ATnd5W5S_FV9LnYIeXs4jj7WbFthlDJaMTmhJ_-gL7GmcbrOtpK30MpOs4lqd5RLMefk13aTwoDpzTKwW_V2p95Obu27eiumpeOP6Po4-NXnyh_XE8B3QJ5G45NPf__-T-xvk_6OVg</recordid><startdate>20220201</startdate><enddate>20220201</enddate><creator>Yamana, Satoshi</creator><creator>Shibata, Kensuke</creator><creator>Hasegawa, Eiichi</creator><creator>Arima, Mitsuru</creator><creator>Shimokawa, Shotaro</creator><creator>Yawata, Nobuyo</creator><creator>Takeda, Atsunobu</creator><creator>Yamasaki, Sho</creator><creator>Sonoda, Koh-Hei</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8794-7368</orcidid></search><sort><creationdate>20220201</creationdate><title>Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity</title><author>Yamana, Satoshi ; Shibata, Kensuke ; Hasegawa, Eiichi ; Arima, Mitsuru ; Shimokawa, Shotaro ; Yawata, Nobuyo ; Takeda, Atsunobu ; Yamasaki, Sho ; Sonoda, Koh-Hei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-54a8218996c418751815c79cc621b9ce818067f61076505e768d33e7e7e7dca03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Allergology</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Autoimmune diseases</topic><topic>Autoimmunity</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Experimental autoimmune uveitis</topic><topic>Experimental autoimmune uveoretinitis</topic><topic>Eye - pathology</topic><topic>Gastroenterology</topic><topic>Humans</topic><topic>Immunology</topic><topic>Inflammation</topic><topic>Interleukin 22</topic><topic>Lymphocytes T</topic><topic>Metabolites</topic><topic>Mice</topic><topic>Mucosa</topic><topic>Mucosal-Associated Invariant T Cells - metabolism</topic><topic>Neuroprotection</topic><topic>Pathology</topic><topic>Retina</topic><topic>Single-cell protein</topic><topic>Uveitis</topic><topic>Uveitis - metabolism</topic><topic>Uveitis - pathology</topic><topic>Uveomeningoencephalitic Syndrome</topic><topic>Visual perception</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamana, Satoshi</creatorcontrib><creatorcontrib>Shibata, Kensuke</creatorcontrib><creatorcontrib>Hasegawa, Eiichi</creatorcontrib><creatorcontrib>Arima, Mitsuru</creatorcontrib><creatorcontrib>Shimokawa, Shotaro</creatorcontrib><creatorcontrib>Yawata, Nobuyo</creatorcontrib><creatorcontrib>Takeda, Atsunobu</creatorcontrib><creatorcontrib>Yamasaki, Sho</creatorcontrib><creatorcontrib>Sonoda, Koh-Hei</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Mucosal immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamana, Satoshi</au><au>Shibata, Kensuke</au><au>Hasegawa, Eiichi</au><au>Arima, Mitsuru</au><au>Shimokawa, Shotaro</au><au>Yawata, Nobuyo</au><au>Takeda, Atsunobu</au><au>Yamasaki, Sho</au><au>Sonoda, Koh-Hei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity</atitle><jtitle>Mucosal immunology</jtitle><stitle>Mucosal Immunol</stitle><addtitle>Mucosal Immunol</addtitle><date>2022-02-01</date><risdate>2022</risdate><volume>15</volume><issue>2</issue><spage>351</spage><epage>361</epage><pages>351-361</pages><issn>1933-0219</issn><eissn>1935-3456</eissn><abstract>Autoimmune uveitis is a sight-threatening disease induced by pathogenic T cells that recognize retinal antigens; it is observed in disorders including Vogt–Koyanagi–Harada disease (VKH). The roles of specific T cell subsets and their therapeutic potential against autoimmune uveitis are not fully understood. Here we conducted multi-parametric single-cell protein quantification which shows that the frequency of CD161
high
TRAV1-2
+
mucosal-associated invariant T (MAIT) cells that recognize vitamin B2 metabolite-based antigens is decreased in relapsing VKH patients compared to individuals without active ocular inflammation. An experimental autoimmune uveitis (EAU) mouse model revealed that genetic depletion of MAIT cells reduced the expression of
interleukin
(
Il
)
22
and exacerbated retinal pathology. Reduced IL-22 levels were commonly observed in patients with relapsing VKH compared to individuals without active ocular inflammation. Both mouse and human MAIT cells produced IL-22 upon stimulation with their antigenic metabolite in vitro. An intravitreal administration of the antigenic metabolite into EAU mice induced retinal MAIT cell expansion and enhanced the expressions of
Il22
, as well as its downstream genes related to anti-inflammatory and neuroprotective effects, leading to an improvement in both retinal pathology and visual function. Taken together, we demonstrate that a metabolite-driven approach targeting MAIT cells has therapeutic potential against autoimmune uveitis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>34775490</pmid><doi>10.1038/s41385-021-00469-5</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-8794-7368</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| subjects | Allergology Animals Antibodies Antigens Autoimmune diseases Autoimmunity Biomedical and Life Sciences Biomedicine Experimental autoimmune uveitis Experimental autoimmune uveoretinitis Eye - pathology Gastroenterology Humans Immunology Inflammation Interleukin 22 Lymphocytes T Metabolites Mice Mucosa Mucosal-Associated Invariant T Cells - metabolism Neuroprotection Pathology Retina Single-cell protein Uveitis Uveitis - metabolism Uveitis - pathology Uveomeningoencephalitic Syndrome Visual perception |
| title | Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity |
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