A68 INVESTIGATING THE ROLE OF INTESTINAL EPITHELIAL CELL NF-κβ SIGNALLING IN CD8 T CELL RESPONSE TO MURINE NOROVIRUS
Bibliographic record
Abstract
The intestinal lumen constitutes the site of highest contact between a mucosal surface and non-self matter. IECs serve dual functions: acting as a physical barrier, as well as working in conjunction with innate and adaptive immune cells to form a dynamic sensory organ that surveys luminal contents and responds to threats. Nuclear Factor kappa β (NF-κβ) is a major regulator of inflammation in response to physical damage and pathogenic events. NF-κβ signalling can be induced through Inhibitor of Kappa Kinase α or β (IKKα and IKKβ). Previous research has shown differential effects between IEC NF-κβ induction through IKKα or IKKβ in DSS-induced colitis and in response to intestinal infections with bacteria or helminths. Currently, the significance of IEC NF-κβ signalling through IKKα and IKKβ during intestinal viral infection is unknown. This research will examine the impact of IKKα or IKKβ ablation specifically in IECs on the magnitude and localization of CD8 T cell responses to acute Murine Norovirus (MNV). Virus specific CD8 T cells will be quantified and phenotypically characterized by flow cytometry. Immunofluorescent microscopy will be used to examine the localization of responding CD8 T cells. It is anticipated that the combination of these complementary techniques will highlight the importance of IEC signalling during immune responses in this highly dynamic environment. Mice lacking either IKKα or IKKβ in IECs were injected with virus-specific mCherry+ CD8 T cells and then infected with MNV-CW3, a strain that recapitulates characteristics of human Norovirus infection, including intestinal exposure, systemic spread, and acute clearance. At the peak of the antiviral T cell response (day 8), intestines and spleen were harvested and immune populations were analyzed. A combination of flow cytometry and immunofluorescent microscopy were used to characterize the CD8 T cell response in terms of individual cell phenotype and localization, respectively. Flow cytometry data from spleen and intestinal CD8 T cells demonstrate a decreased number and impaired activation of antiviral CD8 T in mice lacking IEC intrinsic IKKα. This finding identifies a role for IEC NF-κβ signalling in shaping the viral response by influencing activation of responding CD8 T cell population in response to intestinal viral infection. Furthermore, the systemic deficiency in responding cell numbers suggests that signalling from the intestinal epithelium is critical not just for local responses but also in organism wide immunity to intestinal pathogens. CIHR
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".