Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation
Mucosal tissues are constantly in direct contact with diverse beneficial and pathogenic microbes, highlighting the need for orchestrating complex microbial signals to sustain effective host defense. Here, we show an essential role for intestinal epithelial cell expression of histone deacetylase 3 (H...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-05-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717305405 |
| _version_ | 1798045723341619200 |
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| author | Nazanin Navabi Jordan Whitt Shu-en Wu Vivienne Woo Jessica Moncivaiz Michael B. Jordan Bruce A. Vallance Sing Sing Way Theresa Alenghat |
| author_facet | Nazanin Navabi Jordan Whitt Shu-en Wu Vivienne Woo Jessica Moncivaiz Michael B. Jordan Bruce A. Vallance Sing Sing Way Theresa Alenghat |
| author_sort | Nazanin Navabi |
| collection | DOAJ |
| description | Mucosal tissues are constantly in direct contact with diverse beneficial and pathogenic microbes, highlighting the need for orchestrating complex microbial signals to sustain effective host defense. Here, we show an essential role for intestinal epithelial cell expression of histone deacetylase 3 (HDAC3) in responding to pathogenic microbes and activating protective innate immunity. Mice lacking HDAC3 in intestinal epithelial cells were more susceptible to Citrobacter rodentium when under tonic stimulation by the commensal microbiota. This impaired host defense reflected significantly decreased IFNγ production by intraepithelial CD8+ T cells early during infection. Further, HDAC3 was necessary for infection-induced epithelial expression of the IFNγ-inducing factor IL-18, and administration of IL-18 restored IFNγ activity to resident CD8+ T cells and reduced infection. Thus, HDAC3 mediates communication between intestinal epithelial cells and resident lymphocytes, revealing that epithelial priming by an epigenetic modifier may direct mucosal regulation of host defense against pathogenic microbes. |
| first_indexed | 2024-04-11T23:26:57Z |
| format | Article |
| id | doaj.art-cf9c6531f7a7493785cf44c32e72b6ad |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-11T23:26:57Z |
| publishDate | 2017-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-cf9c6531f7a7493785cf44c32e72b6ad2022-12-22T03:57:18ZengElsevierCell Reports2211-12472017-05-011961165117510.1016/j.celrep.2017.04.046Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte ActivationNazanin Navabi0Jordan Whitt1Shu-en Wu2Vivienne Woo3Jessica Moncivaiz4Michael B. Jordan5Bruce A. Vallance6Sing Sing Way7Theresa Alenghat8Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Gastroenterology, Department of Pediatrics, BC Children’s Hospital Research Institute (BCCHRI), University of British Columbia, Vancouver, BC V6H 3V4, CanadaDivision of Infectious Diseases and Perinatal Institute, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USADivision of Immunobiology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USAMucosal tissues are constantly in direct contact with diverse beneficial and pathogenic microbes, highlighting the need for orchestrating complex microbial signals to sustain effective host defense. Here, we show an essential role for intestinal epithelial cell expression of histone deacetylase 3 (HDAC3) in responding to pathogenic microbes and activating protective innate immunity. Mice lacking HDAC3 in intestinal epithelial cells were more susceptible to Citrobacter rodentium when under tonic stimulation by the commensal microbiota. This impaired host defense reflected significantly decreased IFNγ production by intraepithelial CD8+ T cells early during infection. Further, HDAC3 was necessary for infection-induced epithelial expression of the IFNγ-inducing factor IL-18, and administration of IL-18 restored IFNγ activity to resident CD8+ T cells and reduced infection. Thus, HDAC3 mediates communication between intestinal epithelial cells and resident lymphocytes, revealing that epithelial priming by an epigenetic modifier may direct mucosal regulation of host defense against pathogenic microbes.http://www.sciencedirect.com/science/article/pii/S2211124717305405infectionintestinemicrobiotaHDAC3epigeneticmucosal immunologyepithelialdefenseinnate |
| spellingShingle | Nazanin Navabi Jordan Whitt Shu-en Wu Vivienne Woo Jessica Moncivaiz Michael B. Jordan Bruce A. Vallance Sing Sing Way Theresa Alenghat Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation Cell Reports infection intestine microbiota HDAC3 epigenetic mucosal immunology epithelial defense innate |
| title | Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation |
| title_full | Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation |
| title_fullStr | Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation |
| title_full_unstemmed | Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation |
| title_short | Epithelial Histone Deacetylase 3 Instructs Intestinal Immunity by Coordinating Local Lymphocyte Activation |
| title_sort | epithelial histone deacetylase 3 instructs intestinal immunity by coordinating local lymphocyte activation |
| topic | infection intestine microbiota HDAC3 epigenetic mucosal immunology epithelial defense innate |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717305405 |
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