Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes
Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2018-09, Vol.67 (9), p.1858-1866 |
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| creator | Anquetil, Florence Mondanelli, Giada Gonzalez, Nathaly Rodriguez Calvo, Teresa Zapardiel Gonzalo, Jose Krogvold, Lars Dahl-Jørgensen, Knut Van den Eynde, Benoit Orabona, Ciriana Grohmann, Ursula von Herrath, Matthias G |
| description | Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donors without diabetes, less IDO1 was expressed in insulin-containing islets from double autoantibody-positive donors and patients with recent-onset T1D, although it was virtually absent in insulin-deficient islets from donors with T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with multiple autoantibodies, prior to β-cell demise. IDO1 impairment might therefore contribute to β-cell demise and could potentially emerge as a promising therapeutic target. |
| doi_str_mv | 10.2337/db17-1281 |
| format | Article |
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In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donors without diabetes, less IDO1 was expressed in insulin-containing islets from double autoantibody-positive donors and patients with recent-onset T1D, although it was virtually absent in insulin-deficient islets from donors with T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with multiple autoantibodies, prior to β-cell demise. IDO1 impairment might therefore contribute to β-cell demise and could potentially emerge as a promising therapeutic target.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db17-1281</identifier><identifier>PMID: 29945890</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Adolescent ; Adult ; Aged ; Autoantibodies ; Autoantibodies - metabolism ; Autoimmune Diseases - immunology ; Autoimmune Diseases - metabolism ; Autoimmune Diseases - pathology ; Autoimmune Diseases - physiopathology ; Autoimmunity ; Beta cells ; Cadaver ; Cells ; Cohort Studies ; Cross-Sectional Studies ; Diabetes ; Diabetes mellitus (insulin dependent) ; Diabetes Mellitus, Type 1 - immunology ; Diabetes Mellitus, Type 1 - metabolism ; Diabetes Mellitus, Type 1 - pathology ; Diabetes Mellitus, Type 1 - physiopathology ; Diabetes Mellitus, Type 2 - immunology ; Diabetes Mellitus, Type 2 - metabolism ; Diabetes Mellitus, Type 2 - pathology ; Diabetes Mellitus, Type 2 - physiopathology ; Dioxygenase ; Disease Progression ; Down-Regulation ; Enzymes ; Female ; Fluorescent Antibody Technique, Indirect ; Humans ; Immunoregulation ; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism ; Insulin ; Insulin - metabolism ; Insulin-Secreting Cells - enzymology ; Insulin-Secreting Cells - immunology ; Insulin-Secreting Cells - metabolism ; Insulin-Secreting Cells - pathology ; Localization ; Male ; Middle Aged ; Pancreas ; Pathophysiology ; Prediabetic State - immunology ; Prediabetic State - metabolism ; Prediabetic State - pathology ; Prediabetic State - physiopathology ; Protein Transport ; Therapeutic applications ; Young Adult</subject><ispartof>Diabetes (New York, N.Y.), 2018-09, Vol.67 (9), p.1858-1866</ispartof><rights>2018 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association Sep 1, 2018</rights><rights>2018 by the American Diabetes Association. 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2481-9cc320904155bb73f63202609e466fa4626a7859bff9c55895220400845cca6c3</citedby><cites>FETCH-LOGICAL-c2481-9cc320904155bb73f63202609e466fa4626a7859bff9c55895220400845cca6c3</cites><orcidid>0000-0002-4926-9866 ; 0000-0003-3113-0572</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110313/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110313/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27922,27923,53789,53791</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29945890$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anquetil, Florence</creatorcontrib><creatorcontrib>Mondanelli, Giada</creatorcontrib><creatorcontrib>Gonzalez, Nathaly</creatorcontrib><creatorcontrib>Rodriguez Calvo, Teresa</creatorcontrib><creatorcontrib>Zapardiel Gonzalo, Jose</creatorcontrib><creatorcontrib>Krogvold, Lars</creatorcontrib><creatorcontrib>Dahl-Jørgensen, Knut</creatorcontrib><creatorcontrib>Van den Eynde, Benoit</creatorcontrib><creatorcontrib>Orabona, Ciriana</creatorcontrib><creatorcontrib>Grohmann, Ursula</creatorcontrib><creatorcontrib>von Herrath, Matthias G</creatorcontrib><title>Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donors without diabetes, less IDO1 was expressed in insulin-containing islets from double autoantibody-positive donors and patients with recent-onset T1D, although it was virtually absent in insulin-deficient islets from donors with T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with multiple autoantibodies, prior to β-cell demise. IDO1 impairment might therefore contribute to β-cell demise and could potentially emerge as a promising therapeutic target.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Autoantibodies</subject><subject>Autoantibodies - metabolism</subject><subject>Autoimmune Diseases - immunology</subject><subject>Autoimmune Diseases - metabolism</subject><subject>Autoimmune Diseases - pathology</subject><subject>Autoimmune Diseases - physiopathology</subject><subject>Autoimmunity</subject><subject>Beta cells</subject><subject>Cadaver</subject><subject>Cells</subject><subject>Cohort Studies</subject><subject>Cross-Sectional Studies</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes Mellitus, Type 1 - immunology</subject><subject>Diabetes Mellitus, Type 1 - metabolism</subject><subject>Diabetes Mellitus, Type 1 - pathology</subject><subject>Diabetes Mellitus, Type 1 - physiopathology</subject><subject>Diabetes Mellitus, Type 2 - immunology</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diabetes Mellitus, Type 2 - pathology</subject><subject>Diabetes Mellitus, Type 2 - physiopathology</subject><subject>Dioxygenase</subject><subject>Disease Progression</subject><subject>Down-Regulation</subject><subject>Enzymes</subject><subject>Female</subject><subject>Fluorescent Antibody Technique, Indirect</subject><subject>Humans</subject><subject>Immunoregulation</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</subject><subject>Insulin</subject><subject>Insulin - metabolism</subject><subject>Insulin-Secreting Cells - enzymology</subject><subject>Insulin-Secreting Cells - immunology</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Insulin-Secreting Cells - pathology</subject><subject>Localization</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Pancreas</subject><subject>Pathophysiology</subject><subject>Prediabetic State - immunology</subject><subject>Prediabetic State - metabolism</subject><subject>Prediabetic State - pathology</subject><subject>Prediabetic State - physiopathology</subject><subject>Protein Transport</subject><subject>Therapeutic applications</subject><subject>Young Adult</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUctK7DAYDnJEx8vCFzgEzkYX1VzatNkIMuMNBnQxgruQZv46kbapSSuKb-WD-EymeOEoWYQkX77_uyC0R8kh4zw_WpY0Tygr6BqaUMllwll--wdNCKEsobnMN9FWCPeEEBHXBtpkUqZZIckEvcxdCNhV-HJ2RfHpU-chBOtafOZdgy-GRrf4WrfGg-6twW-vyRTqOuBrDwaWEPBiBdbjGYTeD6Yff84Gb9s73K8gXj9C7boG2n6csXjuAFM8s7qEHsIOWq90HWD3c99GN2eni-lFMr86v5yezBPD0oIm0hjOiCQpzbKyzHkl4pEJIiEVotKpYELnRSbLqpImi7YyxkhKSJFmxmhh-DY6_uDthrKBpYlqvK5V522j_bNy2qqfL61dqTv3qASlhFMeCfY_Cbx7GKJV1dhgYg66BTcExWKqhZAizSL03y_ovRt8G-0pRkmRcymYjKiDD5TxMX4P1bcYStRYqRorVWOlEfv3f_XfyK8O-TuLg5tw</recordid><startdate>201809</startdate><enddate>201809</enddate><creator>Anquetil, Florence</creator><creator>Mondanelli, Giada</creator><creator>Gonzalez, Nathaly</creator><creator>Rodriguez Calvo, Teresa</creator><creator>Zapardiel Gonzalo, Jose</creator><creator>Krogvold, Lars</creator><creator>Dahl-Jørgensen, Knut</creator><creator>Van den Eynde, Benoit</creator><creator>Orabona, Ciriana</creator><creator>Grohmann, Ursula</creator><creator>von Herrath, Matthias G</creator><general>American Diabetes Association</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>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4926-9866</orcidid><orcidid>https://orcid.org/0000-0003-3113-0572</orcidid></search><sort><creationdate>201809</creationdate><title>Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes</title><author>Anquetil, Florence ; Mondanelli, Giada ; Gonzalez, Nathaly ; Rodriguez Calvo, Teresa ; Zapardiel Gonzalo, Jose ; Krogvold, Lars ; Dahl-Jørgensen, Knut ; Van den Eynde, Benoit ; Orabona, Ciriana ; Grohmann, Ursula ; von Herrath, Matthias G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2481-9cc320904155bb73f63202609e466fa4626a7859bff9c55895220400845cca6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Autoantibodies</topic><topic>Autoantibodies - metabolism</topic><topic>Autoimmune Diseases - immunology</topic><topic>Autoimmune Diseases - metabolism</topic><topic>Autoimmune Diseases - pathology</topic><topic>Autoimmune Diseases - physiopathology</topic><topic>Autoimmunity</topic><topic>Beta cells</topic><topic>Cadaver</topic><topic>Cells</topic><topic>Cohort Studies</topic><topic>Cross-Sectional Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes Mellitus, Type 1 - immunology</topic><topic>Diabetes Mellitus, Type 1 - metabolism</topic><topic>Diabetes Mellitus, Type 1 - pathology</topic><topic>Diabetes Mellitus, Type 1 - physiopathology</topic><topic>Diabetes Mellitus, Type 2 - immunology</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diabetes Mellitus, Type 2 - pathology</topic><topic>Diabetes Mellitus, Type 2 - physiopathology</topic><topic>Dioxygenase</topic><topic>Disease Progression</topic><topic>Down-Regulation</topic><topic>Enzymes</topic><topic>Female</topic><topic>Fluorescent Antibody Technique, Indirect</topic><topic>Humans</topic><topic>Immunoregulation</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism</topic><topic>Insulin</topic><topic>Insulin - metabolism</topic><topic>Insulin-Secreting Cells - enzymology</topic><topic>Insulin-Secreting Cells - immunology</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Insulin-Secreting Cells - pathology</topic><topic>Localization</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Pancreas</topic><topic>Pathophysiology</topic><topic>Prediabetic State - immunology</topic><topic>Prediabetic State - metabolism</topic><topic>Prediabetic State - pathology</topic><topic>Prediabetic State - physiopathology</topic><topic>Protein Transport</topic><topic>Therapeutic applications</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anquetil, Florence</creatorcontrib><creatorcontrib>Mondanelli, Giada</creatorcontrib><creatorcontrib>Gonzalez, Nathaly</creatorcontrib><creatorcontrib>Rodriguez Calvo, Teresa</creatorcontrib><creatorcontrib>Zapardiel Gonzalo, Jose</creatorcontrib><creatorcontrib>Krogvold, Lars</creatorcontrib><creatorcontrib>Dahl-Jørgensen, Knut</creatorcontrib><creatorcontrib>Van den Eynde, Benoit</creatorcontrib><creatorcontrib>Orabona, Ciriana</creatorcontrib><creatorcontrib>Grohmann, Ursula</creatorcontrib><creatorcontrib>von Herrath, Matthias G</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 Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anquetil, Florence</au><au>Mondanelli, Giada</au><au>Gonzalez, Nathaly</au><au>Rodriguez Calvo, Teresa</au><au>Zapardiel Gonzalo, Jose</au><au>Krogvold, Lars</au><au>Dahl-Jørgensen, Knut</au><au>Van den Eynde, Benoit</au><au>Orabona, Ciriana</au><au>Grohmann, Ursula</au><au>von Herrath, Matthias G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2018-09</date><risdate>2018</risdate><volume>67</volume><issue>9</issue><spage>1858</spage><epage>1866</epage><pages>1858-1866</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Indoleamine 2,3 dioxygenase-1 (IDO1) is a powerful immunoregulatory enzyme that is deficient in patients with type 1 diabetes (T1D). In this study, we present the first systematic evaluation of IDO1 expression and localization in human pancreatic tissue. Although IDO1 was constitutively expressed in β-cells from donors without diabetes, less IDO1 was expressed in insulin-containing islets from double autoantibody-positive donors and patients with recent-onset T1D, although it was virtually absent in insulin-deficient islets from donors with T1D. Scatter plot analysis suggested that IDO1 decay occurred in individuals with multiple autoantibodies, prior to β-cell demise. IDO1 impairment might therefore contribute to β-cell demise and could potentially emerge as a promising therapeutic target.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>29945890</pmid><doi>10.2337/db17-1281</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-4926-9866</orcidid><orcidid>https://orcid.org/0000-0003-3113-0572</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Autoantibodies Autoantibodies - metabolism Autoimmune Diseases - immunology Autoimmune Diseases - metabolism Autoimmune Diseases - pathology Autoimmune Diseases - physiopathology Autoimmunity Beta cells Cadaver Cells Cohort Studies Cross-Sectional Studies Diabetes Diabetes mellitus (insulin dependent) Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - metabolism Diabetes Mellitus, Type 1 - pathology Diabetes Mellitus, Type 1 - physiopathology Diabetes Mellitus, Type 2 - immunology Diabetes Mellitus, Type 2 - metabolism Diabetes Mellitus, Type 2 - pathology Diabetes Mellitus, Type 2 - physiopathology Dioxygenase Disease Progression Down-Regulation Enzymes Female Fluorescent Antibody Technique, Indirect Humans Immunoregulation Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism Insulin Insulin - metabolism Insulin-Secreting Cells - enzymology Insulin-Secreting Cells - immunology Insulin-Secreting Cells - metabolism Insulin-Secreting Cells - pathology Localization Male Middle Aged Pancreas Pathophysiology Prediabetic State - immunology Prediabetic State - metabolism Prediabetic State - pathology Prediabetic State - physiopathology Protein Transport Therapeutic applications Young Adult |
| title | Loss of IDO1 Expression From Human Pancreatic β-Cells Precedes Their Destruction During the Development of Type 1 Diabetes |
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