Loading…

Single cell transcriptomic analysis of Graves’ disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity

The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and ad...

Full description

Saved in:
Bibliographic Details
Published in:Journal of autoimmunity 2023-09, Vol.139, p.103072-103072, Article 103072
Main Authors: Álvarez-Sierra, Daniel, Rodríguez-Grande, Jorge, Gómez-Brey, Aroa, Bello, Irene, Caubet, Enric, González, Óscar, Zafón, Carles, Iglesias, Carmela, Moreno, Pablo, Ruiz, Núria, Marín-Sánchez, Ana, Colobran, Roger, Pujol-Borrell, Ricardo
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3
cites cdi_FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3
container_end_page 103072
container_issue
container_start_page 103072
container_title Journal of autoimmunity
container_volume 139
creator Álvarez-Sierra, Daniel
Rodríguez-Grande, Jorge
Gómez-Brey, Aroa
Bello, Irene
Caubet, Enric
González, Óscar
Zafón, Carles
Iglesias, Carmela
Moreno, Pablo
Ruiz, Núria
Marín-Sánchez, Ana
Colobran, Roger
Pujol-Borrell, Ricardo
description The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves’ disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas. •Thyroid transcriptional changes are driven by IFN II response signature.•Proinflammatory cytokines and chemokines are expressed in control thyroids.•Thyrocytes in autoimmune expressed HLA genes but no costimulatory molecules.•Immunoregulatory genes are expressed by control and autoimmune thyrocytes.•Wound healing and structural signaling pathways are enhanced in autoimmunity.
doi_str_mv 10.1016/j.jaut.2023.103072
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2827923997</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0896841123000811</els_id><sourcerecordid>2827923997</sourcerecordid><originalsourceid>FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3</originalsourceid><addsrcrecordid>eNp9UU1vEzEQXSoQDYU_wAH5yGWDP7LeXYlLVUFbKRIH4Gw59iQ48trL2Bs1N_4Gf49fgjdpOXKa0ei9N_PmVdVbRpeMMvlhv9zrKS855aIMBG35RbVgtG_qnjXt82pBu17W3Yqxy-pVSntKGWua5mV1KVohJGV88eziqws7D8SA9ySjDsmgG3McnCE6aH9MLpG4JbeoD5D-_PpNrEugE5D844jRWbLzOthEEA6gfSpjIBuM2hI3DFOICLvJ6xzxSMaYIWSn_Sz4RN9G750pECz7LEkZ41AQ8z3pNHHD6B2Ungx6H7Esql3IgCNC1tnFcFYDgrH4KL3eABYjmdytr4nxOiVyf0_goRBSmvEukPK3eLrP5ePr6sW2XA5vHutV9f3zp283d_X6y-39zfW6NqKRubZMdvz0wI2VzPSS09bwtmt6oXkvhTGrjgrZdKztGZfayJXl1hjerVrdm424qt6fdUeMPydIWQ0uzT51gDglxTve9lz0fVug_Aw1GFNC2KoR3aDxqBhVc_Zqr-bs1Zy9OmdfSO8e9afNAPYf5SnsAvh4BkBxeXCAKhkHwYB1CCYrG93_9P8C7SrG0A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2827923997</pqid></control><display><type>article</type><title>Single cell transcriptomic analysis of Graves’ disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity</title><source>Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list)</source><creator>Álvarez-Sierra, Daniel ; Rodríguez-Grande, Jorge ; Gómez-Brey, Aroa ; Bello, Irene ; Caubet, Enric ; González, Óscar ; Zafón, Carles ; Iglesias, Carmela ; Moreno, Pablo ; Ruiz, Núria ; Marín-Sánchez, Ana ; Colobran, Roger ; Pujol-Borrell, Ricardo</creator><creatorcontrib>Álvarez-Sierra, Daniel ; Rodríguez-Grande, Jorge ; Gómez-Brey, Aroa ; Bello, Irene ; Caubet, Enric ; González, Óscar ; Zafón, Carles ; Iglesias, Carmela ; Moreno, Pablo ; Ruiz, Núria ; Marín-Sánchez, Ana ; Colobran, Roger ; Pujol-Borrell, Ricardo</creatorcontrib><description>The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves’ disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas. •Thyroid transcriptional changes are driven by IFN II response signature.•Proinflammatory cytokines and chemokines are expressed in control thyroids.•Thyrocytes in autoimmune expressed HLA genes but no costimulatory molecules.•Immunoregulatory genes are expressed by control and autoimmune thyrocytes.•Wound healing and structural signaling pathways are enhanced in autoimmunity.</description><identifier>ISSN: 0896-8411</identifier><identifier>EISSN: 1095-9157</identifier><identifier>DOI: 10.1016/j.jaut.2023.103072</identifier><identifier>PMID: 37336012</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Adaptative immunity ; Peripheral tolerance ; Thyroid autoimmunity</subject><ispartof>Journal of autoimmunity, 2023-09, Vol.139, p.103072-103072, Article 103072</ispartof><rights>2023 Elsevier Ltd</rights><rights>Copyright © 2023 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3</citedby><cites>FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37336012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Álvarez-Sierra, Daniel</creatorcontrib><creatorcontrib>Rodríguez-Grande, Jorge</creatorcontrib><creatorcontrib>Gómez-Brey, Aroa</creatorcontrib><creatorcontrib>Bello, Irene</creatorcontrib><creatorcontrib>Caubet, Enric</creatorcontrib><creatorcontrib>González, Óscar</creatorcontrib><creatorcontrib>Zafón, Carles</creatorcontrib><creatorcontrib>Iglesias, Carmela</creatorcontrib><creatorcontrib>Moreno, Pablo</creatorcontrib><creatorcontrib>Ruiz, Núria</creatorcontrib><creatorcontrib>Marín-Sánchez, Ana</creatorcontrib><creatorcontrib>Colobran, Roger</creatorcontrib><creatorcontrib>Pujol-Borrell, Ricardo</creatorcontrib><title>Single cell transcriptomic analysis of Graves’ disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity</title><title>Journal of autoimmunity</title><addtitle>J Autoimmun</addtitle><description>The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves’ disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas. •Thyroid transcriptional changes are driven by IFN II response signature.•Proinflammatory cytokines and chemokines are expressed in control thyroids.•Thyrocytes in autoimmune expressed HLA genes but no costimulatory molecules.•Immunoregulatory genes are expressed by control and autoimmune thyrocytes.•Wound healing and structural signaling pathways are enhanced in autoimmunity.</description><subject>Adaptative immunity</subject><subject>Peripheral tolerance</subject><subject>Thyroid autoimmunity</subject><issn>0896-8411</issn><issn>1095-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9UU1vEzEQXSoQDYU_wAH5yGWDP7LeXYlLVUFbKRIH4Gw59iQ48trL2Bs1N_4Gf49fgjdpOXKa0ei9N_PmVdVbRpeMMvlhv9zrKS855aIMBG35RbVgtG_qnjXt82pBu17W3Yqxy-pVSntKGWua5mV1KVohJGV88eziqws7D8SA9ySjDsmgG3McnCE6aH9MLpG4JbeoD5D-_PpNrEugE5D844jRWbLzOthEEA6gfSpjIBuM2hI3DFOICLvJ6xzxSMaYIWSn_Sz4RN9G750pECz7LEkZ41AQ8z3pNHHD6B2Ungx6H7Esql3IgCNC1tnFcFYDgrH4KL3eABYjmdytr4nxOiVyf0_goRBSmvEukPK3eLrP5ePr6sW2XA5vHutV9f3zp283d_X6y-39zfW6NqKRubZMdvz0wI2VzPSS09bwtmt6oXkvhTGrjgrZdKztGZfayJXl1hjerVrdm424qt6fdUeMPydIWQ0uzT51gDglxTve9lz0fVug_Aw1GFNC2KoR3aDxqBhVc_Zqr-bs1Zy9OmdfSO8e9afNAPYf5SnsAvh4BkBxeXCAKhkHwYB1CCYrG93_9P8C7SrG0A</recordid><startdate>20230901</startdate><enddate>20230901</enddate><creator>Álvarez-Sierra, Daniel</creator><creator>Rodríguez-Grande, Jorge</creator><creator>Gómez-Brey, Aroa</creator><creator>Bello, Irene</creator><creator>Caubet, Enric</creator><creator>González, Óscar</creator><creator>Zafón, Carles</creator><creator>Iglesias, Carmela</creator><creator>Moreno, Pablo</creator><creator>Ruiz, Núria</creator><creator>Marín-Sánchez, Ana</creator><creator>Colobran, Roger</creator><creator>Pujol-Borrell, Ricardo</creator><general>Elsevier Ltd</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20230901</creationdate><title>Single cell transcriptomic analysis of Graves’ disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity</title><author>Álvarez-Sierra, Daniel ; Rodríguez-Grande, Jorge ; Gómez-Brey, Aroa ; Bello, Irene ; Caubet, Enric ; González, Óscar ; Zafón, Carles ; Iglesias, Carmela ; Moreno, Pablo ; Ruiz, Núria ; Marín-Sánchez, Ana ; Colobran, Roger ; Pujol-Borrell, Ricardo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Adaptative immunity</topic><topic>Peripheral tolerance</topic><topic>Thyroid autoimmunity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Álvarez-Sierra, Daniel</creatorcontrib><creatorcontrib>Rodríguez-Grande, Jorge</creatorcontrib><creatorcontrib>Gómez-Brey, Aroa</creatorcontrib><creatorcontrib>Bello, Irene</creatorcontrib><creatorcontrib>Caubet, Enric</creatorcontrib><creatorcontrib>González, Óscar</creatorcontrib><creatorcontrib>Zafón, Carles</creatorcontrib><creatorcontrib>Iglesias, Carmela</creatorcontrib><creatorcontrib>Moreno, Pablo</creatorcontrib><creatorcontrib>Ruiz, Núria</creatorcontrib><creatorcontrib>Marín-Sánchez, Ana</creatorcontrib><creatorcontrib>Colobran, Roger</creatorcontrib><creatorcontrib>Pujol-Borrell, Ricardo</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of autoimmunity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Álvarez-Sierra, Daniel</au><au>Rodríguez-Grande, Jorge</au><au>Gómez-Brey, Aroa</au><au>Bello, Irene</au><au>Caubet, Enric</au><au>González, Óscar</au><au>Zafón, Carles</au><au>Iglesias, Carmela</au><au>Moreno, Pablo</au><au>Ruiz, Núria</au><au>Marín-Sánchez, Ana</au><au>Colobran, Roger</au><au>Pujol-Borrell, Ricardo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single cell transcriptomic analysis of Graves’ disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity</atitle><jtitle>Journal of autoimmunity</jtitle><addtitle>J Autoimmun</addtitle><date>2023-09-01</date><risdate>2023</risdate><volume>139</volume><spage>103072</spage><epage>103072</epage><pages>103072-103072</pages><artnum>103072</artnum><issn>0896-8411</issn><eissn>1095-9157</eissn><abstract>The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway. To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves’ disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes. The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas. •Thyroid transcriptional changes are driven by IFN II response signature.•Proinflammatory cytokines and chemokines are expressed in control thyroids.•Thyrocytes in autoimmune expressed HLA genes but no costimulatory molecules.•Immunoregulatory genes are expressed by control and autoimmune thyrocytes.•Wound healing and structural signaling pathways are enhanced in autoimmunity.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>37336012</pmid><doi>10.1016/j.jaut.2023.103072</doi><tpages>1</tpages></addata></record>
fulltext fulltext
identifier ISSN: 0896-8411
ispartof Journal of autoimmunity, 2023-09, Vol.139, p.103072-103072, Article 103072
issn 0896-8411
1095-9157
language eng
recordid cdi_proquest_miscellaneous_2827923997
source Elsevier:Jisc Collections:Elsevier Read and Publish Agreement 2022-2024:Freedom Collection (Reading list)
subjects Adaptative immunity
Peripheral tolerance
Thyroid autoimmunity
title Single cell transcriptomic analysis of Graves’ disease thyroid glands reveals the broad immunoregulatory potential of thyroid follicular and stromal cells and implies a major re-interpretation of the role of aberrant HLA class II expression in autoimmunity
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T02%3A31%3A39IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Single%20cell%20transcriptomic%20analysis%20of%20Graves%E2%80%99%20disease%20thyroid%20glands%20reveals%20the%20broad%20immunoregulatory%20potential%20of%20thyroid%20follicular%20and%20stromal%20cells%20and%20implies%20a%20major%20re-interpretation%20of%20the%20role%20of%20aberrant%20HLA%20class%20II%20expression%20in%20autoimmunity&rft.jtitle=Journal%20of%20autoimmunity&rft.au=%C3%81lvarez-Sierra,%20Daniel&rft.date=2023-09-01&rft.volume=139&rft.spage=103072&rft.epage=103072&rft.pages=103072-103072&rft.artnum=103072&rft.issn=0896-8411&rft.eissn=1095-9157&rft_id=info:doi/10.1016/j.jaut.2023.103072&rft_dat=%3Cproquest_cross%3E2827923997%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c356t-d168211555bd61c96207c278593a2963cc4803658179126ac64d2dcc2847a9cb3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=2827923997&rft_id=info:pmid/37336012&rfr_iscdi=true