CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells
How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for aut...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/29540 |
| _version_ | 1811252917839069184 |
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| author | Xiaomei Yuan Bi-Huei Yang Yi Dong Asami Yamamura Wenxian Fu |
| author_facet | Xiaomei Yuan Bi-Huei Yang Yi Dong Asami Yamamura Wenxian Fu |
| author_sort | Xiaomei Yuan |
| collection | DOAJ |
| description | How tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells. More importantly, CRIg stabilized the expression of Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The expression of CRIg in TRMs was postnatally regulated by gut microbial signals and metabolites. Thus, environmental cues instruct TRMs to express CRIg, which functions as an immune checkpoint molecule to regulate adaptive immunity and promote immune tolerance. |
| first_indexed | 2024-04-12T16:42:53Z |
| format | Article |
| id | doaj.art-07a64cb60253446e8f5dea8ce1c5841d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:42:53Z |
| publishDate | 2017-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-07a64cb60253446e8f5dea8ce1c5841d2022-12-22T03:24:42ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.29540CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cellsXiaomei Yuan0Bi-Huei Yang1Yi Dong2Asami Yamamura3Wenxian Fu4https://orcid.org/0000-0003-0684-8929Pediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, United StatesPediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, United StatesPediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, United StatesBiomedical Sciences Graduate Program, University of California, San Diego, United StatesPediatric Diabetes Research Center, Department of Pediatrics, University of California, San Diego, United States; Biomedical Sciences Graduate Program, University of California, San Diego, United States; Institute for Diabetes and Metabolic Health, University of California, San Diego, United States; Moores Cancer Center, University of California, San Diego, United StatesHow tissue-resident macrophages (TRM) impact adaptive immune responses remains poorly understood. We report novel mechanisms by which TRMs regulate T cell activities at tissue sites. These mechanisms are mediated by the complement receptor of immunoglobulin family (CRIg). Using animal models for autoimmune type 1 diabetes (T1D), we found that CRIg+ TRMs formed a protective barrier surrounding pancreatic islets. Genetic ablation of CRIg exacerbated islet inflammation and local T cell activation. CRIg exhibited a dual function of attenuating early T cell activation and promoting the differentiation of Foxp3+ regulatory (Treg) cells. More importantly, CRIg stabilized the expression of Foxp3 in Treg cells, by enhancing their responsiveness to interleukin-2. The expression of CRIg in TRMs was postnatally regulated by gut microbial signals and metabolites. Thus, environmental cues instruct TRMs to express CRIg, which functions as an immune checkpoint molecule to regulate adaptive immunity and promote immune tolerance.https://elifesciences.org/articles/29540macrophagesT cellsimmune checkpointimmunological toleranceinflammationCRIg |
| spellingShingle | Xiaomei Yuan Bi-Huei Yang Yi Dong Asami Yamamura Wenxian Fu CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells eLife macrophages T cells immune checkpoint immunological tolerance inflammation CRIg |
| title | CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells |
| title_full | CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells |
| title_fullStr | CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells |
| title_full_unstemmed | CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells |
| title_short | CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells |
| title_sort | crig a tissue resident macrophage specific immune checkpoint molecule promotes immunological tolerance in nod mice via a dual role in effector and regulatory t cells |
| topic | macrophages T cells immune checkpoint immunological tolerance inflammation CRIg |
| url | https://elifesciences.org/articles/29540 |
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