Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells
Antigen presentation via major histocompatibility complex (MHC) class I and class II receptors plays a fundamental role in T cell-mediated adaptive immunity. A dysregulation of this fine-tuned recognition might result in the development of autoimmune diseases such as inflammatory bowel diseases that...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1226809/full |
| _version_ | 1797673970639568896 |
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| author | Julia Diegelmann Julia Diegelmann Stephan Brand Stephan Brand |
| author_facet | Julia Diegelmann Julia Diegelmann Stephan Brand Stephan Brand |
| author_sort | Julia Diegelmann |
| collection | DOAJ |
| description | Antigen presentation via major histocompatibility complex (MHC) class I and class II receptors plays a fundamental role in T cell-mediated adaptive immunity. A dysregulation of this fine-tuned recognition might result in the development of autoimmune diseases such as inflammatory bowel diseases that are characterized by chronic relapsing inflammation of the intestinal tract and a damaged intestinal epithelial barrier. While MHCII receptors are usually expressed by professional antigen presenting cells (APC) only, there is increasing evidence that non-immune cells such as intestinal epithelial cells (IEC) might express MHCII upon stimulation with IFN-γ and thus act as non-professional APC. However, little is known about other factors regulating intestinal epithelial MHC expression. Here, we identify IL-27 as an inducer of different MHCI and MHCII receptor subtypes and the invariant chain (CD74/li) in IEC via the STAT1/IRF1/CIITA axis. CIITA, MHCII, and CD74 expression was significantly increased in IEC from Crohn’s disease (CD) patients with active disease compared to controls or CD patients in remission. IEC phagocytosed and digested external antigens and apoptotic cells. IL-27 strongly stimulated antigen processing via the immunoproteasome in a IRF1-dependent manner. In co-culture experiments, antigen-primed IEC strongly enhanced lymphocyte proliferation and IL-2 secretion, dependent on direct cell-cell contact. IL-27 pretreatment of IEC significantly increased CD4+ T cell proliferation and reduced IL-2 levels in lymphocytes in coculture. In summary, we identified IL-27 as a novel regulator of IEC antigen processing and presentation via MHCI and MHCII receptors, underscoring the importance of IEC as non-professional APC. |
| first_indexed | 2024-03-11T21:53:20Z |
| format | Article |
| id | doaj.art-143614b7fa8d4a849de497fe41d363f9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T21:53:20Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-143614b7fa8d4a849de497fe41d363f92023-09-26T05:54:24ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12268091226809Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cellsJulia Diegelmann0Julia Diegelmann1Stephan Brand2Stephan Brand3Department of Medicine II, Ludwig-Maximilians-Universität (LMU) University Hospital, LMU Munich, Munich, GermanyDepartment of Conservative Dentistry and Periodontology, LMU University Hospital, LMU Munich, Munich, GermanyDepartment of Medicine II, Ludwig-Maximilians-Universität (LMU) University Hospital, LMU Munich, Munich, GermanyDepartment of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen, SwitzerlandAntigen presentation via major histocompatibility complex (MHC) class I and class II receptors plays a fundamental role in T cell-mediated adaptive immunity. A dysregulation of this fine-tuned recognition might result in the development of autoimmune diseases such as inflammatory bowel diseases that are characterized by chronic relapsing inflammation of the intestinal tract and a damaged intestinal epithelial barrier. While MHCII receptors are usually expressed by professional antigen presenting cells (APC) only, there is increasing evidence that non-immune cells such as intestinal epithelial cells (IEC) might express MHCII upon stimulation with IFN-γ and thus act as non-professional APC. However, little is known about other factors regulating intestinal epithelial MHC expression. Here, we identify IL-27 as an inducer of different MHCI and MHCII receptor subtypes and the invariant chain (CD74/li) in IEC via the STAT1/IRF1/CIITA axis. CIITA, MHCII, and CD74 expression was significantly increased in IEC from Crohn’s disease (CD) patients with active disease compared to controls or CD patients in remission. IEC phagocytosed and digested external antigens and apoptotic cells. IL-27 strongly stimulated antigen processing via the immunoproteasome in a IRF1-dependent manner. In co-culture experiments, antigen-primed IEC strongly enhanced lymphocyte proliferation and IL-2 secretion, dependent on direct cell-cell contact. IL-27 pretreatment of IEC significantly increased CD4+ T cell proliferation and reduced IL-2 levels in lymphocytes in coculture. In summary, we identified IL-27 as a novel regulator of IEC antigen processing and presentation via MHCI and MHCII receptors, underscoring the importance of IEC as non-professional APC.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1226809/fullintestinal epithelial cellsIL-27MHC receptorantigen presentationinflammatory bowel diseaseintestinal inflammation |
| spellingShingle | Julia Diegelmann Julia Diegelmann Stephan Brand Stephan Brand Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells Frontiers in Immunology intestinal epithelial cells IL-27 MHC receptor antigen presentation inflammatory bowel disease intestinal inflammation |
| title | Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells |
| title_full | Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells |
| title_fullStr | Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells |
| title_full_unstemmed | Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells |
| title_short | Identification of IL-27 as a novel regulator of major histocompatibility complex class I and class II expression, antigen presentation, and processing in intestinal epithelial cells |
| title_sort | identification of il 27 as a novel regulator of major histocompatibility complex class i and class ii expression antigen presentation and processing in intestinal epithelial cells |
| topic | intestinal epithelial cells IL-27 MHC receptor antigen presentation inflammatory bowel disease intestinal inflammation |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1226809/full |
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