Control of natural killer cell homeostasis by the aryl hydrocarbon receptor
Abstract/Contents
- Abstract
- Natural killer (NK) cells are lymphocytes that recognize and eliminate infected or abnormal cells. Previously thought of as innate immune cells, emerging research has shown the ability of NK cells to have immunologic memory and mediate an enhanced response upon secondary exposure under certain conditions. This ability is heterogenous, with only subsets of NK cells having memory-like features. A liver resident population of NK cells, defined as CD49a+TRAIL+CXCR6+DX5-, has been found to have antigen-specific memory to hapten exposure. Little is known about the transcription factor regulation that differentiates these liver resident memory NK cells from their conventional counterparts. The aryl hydrocarbon receptor (AhR) was recently found to be uniquely expressed in this subset, and for this project, we sought to explore the importance of AhR in the biology of liver resident NK cells. We found that expression of AhR is required for proper maintenance of liver resident NK cells, and in its absence, hapten-specific memory is lost. Furthermore, we found that AhR is required to prevent over proliferation and exhaustion in response to cytokine activation. Finally, we identified several potential molecular targets of AhR which have homeostatic roles, including the ubiquitin ligase subunit ankyrin repeat and SOCS Box containing 2 (Asb2). Taken together, we show that AhR is important for the proper proliferation and survival of NK cells. The homeostatic role of AhR may be what allows for the long term survival of memory NK cells, and utilization of AhR ligands may provide a way to enhance therapeutic NK cells.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Zhang, Luhua | |
|---|---|---|
| Associated with | Stanford University, Program in Immunology. | |
| Primary advisor | Sunwoo, John B | |
| Thesis advisor | Sunwoo, John B | |
| Thesis advisor | Engleman, Edgar G | |
| Thesis advisor | Krams, Sheri Michele | |
| Thesis advisor | Negrin, Robert S | |
| Advisor | Engleman, Edgar G | |
| Advisor | Krams, Sheri Michele | |
| Advisor | Negrin, Robert S |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Luhua Zhang. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Luhua Zhang
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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