Intestinal enteroids as a novel model system for studying MHC class II regulation and function in intestinal epithelial cells
Abstract/Contents
- Abstract
- The intestinal epithelium is a vast surface where dietary antigens, enteric microbes, and the mucosal immune system interact. The intestinal immune system faces a considerable challenge: mediating the timely clearance of pathogens while maintaining tolerance to harmless commensals and dietary antigens. Dysregulation of tolerance leads to disorders such as celiac disease and inflammatory bowel disease. Major Histocompatibility Complex II (MHC-II) plays a critical role in regulating adaptive immunity through the presentation of fragment fragments to CD4 T cells. Small intestinal epithelial cells (IECs) constitutively express MHC-II, though the precise role of epithelial MHC-II in tolerance and immunity is poorly understood. A major obstacle to elucidating the role of IEC MHC-II is the lack of a tractable, physiologically relevant model system. We present a method for inducing MHC class II (MHC-II) in human enteroids, "mini-guts" derived from small intestinal crypt stem cells. The cytokine interferon gamma, typically found at low levels in healthy epithelium, induces MHC-II when provided to IECs along their basolateral surface. We analyzed the intracellular MHC-II peptide-pathway and show that MHC-II molecules in IECs undergo peptide editing before trafficking to the cell surface. We then used a novel polarity reversal approach to demonstrate that MHC-II-expressing enteroids could be reversed such that their apical surface faces outward. This allows for apical antigens and microbes to be added to enteroids in a physiological manner. Our method enables human enteroids to be used for novel in vitro studies into IEC MHC-II regulation and function during health and disease.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Wosen, Jonathan Elias |
|---|---|
| Degree supervisor | Amieva, Manuel |
| Degree supervisor | Mellins, Elizabeth |
| Thesis advisor | Amieva, Manuel |
| Thesis advisor | Mellins, Elizabeth |
| Thesis advisor | Habtezion, Aida |
| Thesis advisor | Khosla, Chaitan, 1964- |
| Degree committee member | Habtezion, Aida |
| Degree committee member | Khosla, Chaitan, 1964- |
| Associated with | Stanford University, Department of Immunology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jonathan Elias Wosen. |
|---|---|
| Note | Submitted to the Department of Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Jonathan Elias Wosen
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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