Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary
Background & Aims: Enteric glial cells express type II major histocompatibility complex (MHC-II) molecules in Crohn’s disease and Chagas disease, but it is unclear whether the expressed molecules are functional. We examined the capabilities of enteric glia to act as an antigen-presenting cel...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X21001235 |
| _version_ | 1819140594080940032 |
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| author | Aaron K. Chow Vladimir Grubišić Brian D. Gulbransen |
| author_facet | Aaron K. Chow Vladimir Grubišić Brian D. Gulbransen |
| author_sort | Aaron K. Chow |
| collection | DOAJ |
| description | Background & Aims: Enteric glial cells express type II major histocompatibility complex (MHC-II) molecules in Crohn’s disease and Chagas disease, but it is unclear whether the expressed molecules are functional. We examined the capabilities of enteric glia to act as an antigen-presenting cell in vivo and whether glial MHC-II has immunomodulatory effects. Methods: We generated Sox10CreERT2;IABfl/fl mice to ablate MHC-II in enteric glia after exposure to tamoxifen. We measured phagocytic activity and autophagy activation to assess potential peptide sources loaded onto glial MHC-II and measured T- and B-lymphocyte activation and serum and colonic tissue cytokine levels to study enteric glial immunomodulatory capabilities. Results: Enteric glia express MHC-II molecules in response to a subclinical dose of interferon-γ and lipopolysaccharide in vivo. Glial MHC-II expression contributes to effective B-lymphocyte and T-lymphocyte activation with marked effects on T-helper cell (Th)17 and regulatory T cell subtypes. No effect on Th1 or Th2 subtypes was observed. Enteric glial MHC-II does not have a major effect on serum or colonic tissue cytokine levels but may influence local cytokine levels. Glial MHC-II expression requires the activation of autophagy pathways, but activating autophagy alone is not sufficient to drive glial MHC-II expression. Conclusions: Enteric glia express MHC-II as a mechanism to tune intestinal immune responses. Glial autophagy is triggered in response to proinflammatory stimuli and induces glial antigen presentation, which functions to modulate the activation of T-lymphocyte subsets involved in tolerance. These observations suggest that enteric glia may express MHC-II to maintain immune homeostasis during inflammatory conditions such as Crohn’s disease. |
| first_indexed | 2024-12-22T11:41:02Z |
| format | Article |
| id | doaj.art-34f94eaa015e4ead8db8f58eb975aac5 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-22T11:41:02Z |
| publishDate | 2021-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-34f94eaa015e4ead8db8f58eb975aac52022-12-21T18:27:17ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2021-01-0112412151237Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummaryAaron K. Chow0Vladimir Grubišić1Brian D. Gulbransen2Department of Physiology, East Lansing, MichiganDepartment of Physiology, East Lansing, MichiganDepartment of Physiology, East Lansing, Michigan; Neuroscience Program, Michigan State University, East Lansing, Michigan; Correspondence Address correspondence to: Brian Gulbransen, PhD, Department of Physiology, Michigan State University, 567 Wilson Road, East Lansing, Michigan 48824. fax: (517) 355-5125.Background & Aims: Enteric glial cells express type II major histocompatibility complex (MHC-II) molecules in Crohn’s disease and Chagas disease, but it is unclear whether the expressed molecules are functional. We examined the capabilities of enteric glia to act as an antigen-presenting cell in vivo and whether glial MHC-II has immunomodulatory effects. Methods: We generated Sox10CreERT2;IABfl/fl mice to ablate MHC-II in enteric glia after exposure to tamoxifen. We measured phagocytic activity and autophagy activation to assess potential peptide sources loaded onto glial MHC-II and measured T- and B-lymphocyte activation and serum and colonic tissue cytokine levels to study enteric glial immunomodulatory capabilities. Results: Enteric glia express MHC-II molecules in response to a subclinical dose of interferon-γ and lipopolysaccharide in vivo. Glial MHC-II expression contributes to effective B-lymphocyte and T-lymphocyte activation with marked effects on T-helper cell (Th)17 and regulatory T cell subtypes. No effect on Th1 or Th2 subtypes was observed. Enteric glial MHC-II does not have a major effect on serum or colonic tissue cytokine levels but may influence local cytokine levels. Glial MHC-II expression requires the activation of autophagy pathways, but activating autophagy alone is not sufficient to drive glial MHC-II expression. Conclusions: Enteric glia express MHC-II as a mechanism to tune intestinal immune responses. Glial autophagy is triggered in response to proinflammatory stimuli and induces glial antigen presentation, which functions to modulate the activation of T-lymphocyte subsets involved in tolerance. These observations suggest that enteric glia may express MHC-II to maintain immune homeostasis during inflammatory conditions such as Crohn’s disease.http://www.sciencedirect.com/science/article/pii/S2352345X21001235Enteric Glial CellAutophagyMajor Histocompatibility Complex Type IIT-Lymphocyte |
| spellingShingle | Aaron K. Chow Vladimir Grubišić Brian D. Gulbransen Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary Cellular and Molecular Gastroenterology and Hepatology Enteric Glial Cell Autophagy Major Histocompatibility Complex Type II T-Lymphocyte |
| title | Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary |
| title_full | Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary |
| title_fullStr | Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary |
| title_full_unstemmed | Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary |
| title_short | Enteric Glia Regulate Lymphocyte Activation via Autophagy-Mediated MHC-II ExpressionSummary |
| title_sort | enteric glia regulate lymphocyte activation via autophagy mediated mhc ii expressionsummary |
| topic | Enteric Glial Cell Autophagy Major Histocompatibility Complex Type II T-Lymphocyte |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X21001235 |
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