A transcriptional switch underlies the pro-and anti-inflammatory activities of afucosylated and sialylated IGG glycoforms
Abstract/Contents
- Abstract
- Antibodies play a crucial role in bridging the gap between the innate and adaptive immune systems by serving as a link that connects these two components of the immune response. They recognize specific antigens on pathogens, facilitating recognition and response by innate immune cells. Additionally, antibodies contribute to immunological memory, allowing the adaptive immune system to mount a faster and more specific response upon re-exposure to the same pathogen. This coordination enhances the overall effectiveness of the immune defense against infections. IgG Fc glycosylation serves as a mechanism to enhance the versatility of antibody function by altering its affinity for specific activating and inhibitory Fc-gamma receptors. This, in turn, regulates Fc-mediated effector functions and influences the innate immune response directed toward target pathogens. However, the precise impact of different IgG glycoforms on immunity in frequently infected sites, such as the lungs, remains unclear. In Chapter I, I review the literature regarding IgG Fc glycosylation, Fc-gamma receptor functions, and the impact of both on human disease outcomes. In Chapter 2, my colleagues and I use mass spectrometry to identify specific IgG glycoforms that correlate with COVID-19 disease trajectories. We identify a correlation between afucosylated IgG abundance and more severe disease outcomes as well as an enrichment of sialylated IgG in protected patient populations. In Chapter 3, we investigate how these glycoforms impact the local immune response within the lungs of Fc-gamma receptor-humanized mice at the functional and transcriptional levels. We identify the transcription factors NF-κB and REST as likely regulators of immune complex-mediated inflammation within the lung. Altogether, we identify a transcriptional switch that underlies the pro- and anti-inflammatory activity of afucosylated and sialylated IgG in the lung mediated by the transcription factors NF-κB and REST that may have relevance in human 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 | 2024; ©2024 |
| Publication date | 2024; 2024 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Gonzalez, Joseph Corral |
|---|---|
| Degree supervisor | Wang, Taia |
| Thesis advisor | Wang, Taia |
| Thesis advisor | Engleman, Edgar G |
| Thesis advisor | Mellins, Elizabeth |
| Thesis advisor | Utz, Paul |
| Degree committee member | Engleman, Edgar G |
| Degree committee member | Mellins, Elizabeth |
| Degree committee member | Utz, Paul |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Program in Immunology |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Joseph Christopher Corral Gonzalez. |
|---|---|
| Note | Submitted to the Program in Immunology. |
| Thesis | Thesis Ph.D. Stanford University 2024. |
| Location | https://purl.stanford.edu/zg343jy6067 |
Access conditions
- Copyright
- © 2024 by Joseph Corral Gonzalez
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
Also listed in
Loading usage metrics...