Abstract
Chronic intermittent hypoxia alters CD8 + expression in the bone marrow of C57BL/6 mice
Physiology (Bethesda, Md.), Vol.39(S1)
05/2024
DOI: 10.1152/physiol.2024.39.S1.1964
Abstract
Abstract only Cytotoxic CD8 + cells are critical in anticancer immune response and have become prevalent in immunotherapies over the past decade. Anti-LAG3/anti-PD1 combined immunotherapies increase the number of CD8 + cells. Moderate to severe sleep apnea increases the risk of cancer-related mortality. Chronic intermittent hypoxia, a feature of sleep apnea, decreases the percentage of perforin-expressing CD8 + cells, impairing cytotoxicity. Our objective is to determine the distribution of Prf1(perforin), LAG3(lymphocyte-activation gene 3), and PDCD1(programmed cell death 1) in C57BL/6 mice exposed to chronic intermittent hypoxia (CIH). We hypothesize that Prf1, PDCD1, and LAG3 will be expressed on three discrete clusters with a higher expression of LAG3 and PDCD1 and lower expression of Prf1 between C57BL/6 mice exposed to chronic intermittent hypoxia and normoxia. Bone marrow from the femur of C57BL/6 mice exposed to chronic intermittent hypoxia or normoxia was harvested. Bone marrow mononuclear cells were isolated, RNA was extracted, and single-cell RNA sequencing was performed. Loupe browser was used to re-cluster and quantify expression for genes of interest. Prf1 and PDCD1 are expressed in CD3 + CD8 − CD4 − cluster and LAG3 is expressed in CD3 − CD8 + CD4 + cluster. LAG3 and Prf1 are present among the top ten genes, while PDCD1 is not in those clusters. Further analysis of the top ten genes of CD3 + CD8 − CD4 − has demonstrated they are a group of natural killer cells. Contradictory to our expectation, Prf1 and PDCD1 are present in CD3 + CD8 − CD4 − cluster while LAG3 is present in CD3 − CD8 + CD4 + cluster. Further analysis is necessary to determine the underlying mechanisms causing these changes. 5R01CA244271-02. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Details
- Title: Subtitle
- Chronic intermittent hypoxia alters CD8 + expression in the bone marrow of C57BL/6 mice
- Creators
- Immaculate Edwin - University of Iowa, Internal MedicineCharles Jedlicka - University of IowaZishan Zhang - Cornell UniversityMikhail Vasilyev - University of IowaAnastasiia Vasileva - University of IowaMichael Tomasson - University of IowaMelissa Bates - University of Iowa
- Resource Type
- Abstract
- Publication Details
- Physiology (Bethesda, Md.), Vol.39(S1)
- Publisher
- AMER PHYSIOLOGICAL SOC
- DOI
- 10.1152/physiol.2024.39.S1.1964
- ISSN
- 1548-9213
- eISSN
- 1548-9221
- Grant note
5R01CA244271-02.
- Language
- English
- Date published
- 05/2024
- Academic Unit
- Health and Human Physiology; Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984648155902771
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