In Vivo Blockade of Murine ARTC2.2 During Cell Preparation Preserves the Vitality and Function of Liver Tissue-Resident Memory T Cells
Open accessAbstract
On murine T cells, GPI-anchored ADP-ribosyltransferase 2.2 (ARTC2.2) ADP-ribosylates the P2X7 ion channel at arginine 125 in response to nicotinamide adenine dinucleotide (NAD+) released during cell preparation. We have previously shown that chronic gating of P2X7 by ADP-ribosylation reduces the vitality and function of regulatory T cells (Tregs) and NKT cells that co-express high levels of ARTC2.2 and P2X7. Here, we evaluated the expression of ARTC2.2 and P2X7 by effector and memory T cells in the liver of naïve mice and after infection with Listeria monocytogenes (Lm). We found that KLRG1–/CD69+ tissue-resident memory T cells (Trm) in the liver of naïve mice and seven weeks after infection with Lm express high levels of ARTC2.2 and P2X7. Isolation of liver Trm and subsequent incubation at 37 °C resulted in cell death of the majority of CD4+ and CD8+ Trm. Injection of the ARTC2.2-blocking nanobody s+16a 30min prior to organ harvesting effectively prevented ADP-ribosylation of P2X7 during cell preparation and thereby prevented NAD-induced cell death (NICD) of the isolated Trm upon subsequent incubation at 37 °C. Consequently, preserving Trm vitality by s+16a injection enabled a highly sensitive in vitro cytokine expression profile analyses of FACS sorted liver Trm. We conclude that in vivo blockade of ARTC2.2 during cell preparation by nanobody s+16a injection represents a valuable strategy to study the role and function of liver Trm in mice.
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Activation of the danger receptor P2RX7 by extracellular NAD or ATP, released by dying cells during processing, can lead to shedding of surface molecules such as CD62L and CD27, the masking of CD8β and the induction of cell death in susceptible cells like Treg, NKT, and Trm cells.
“For example, activation of the danger receptor P2RX7 by extracellular NAD or ATP, released by dying cells during processing, can lead to shedding of surface molecules such as CD62L and CD27, the masking of CD8β and the induction of cell death in susceptible cells like Treg, NKT, and Trm cells [286-288].”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [287]
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Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition)
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- Authors
- Rissiek, B., Lukowiak, M., Raczkowski, F., Magnus, T., Mittrücker, H.-W., & Koch-Nolte, F.
- Affiliations
- University Medical Center Hamburg-Eppendorf (DE)
- Corresponding author
- Rissiek, Björn
- Venue
- Frontiers in Immunology
- Publisher
- Frontiers Media SA
- Published
- 2018-07-09
- Volume
- 9
- Pages
- 1580-1580
- ISSN
- 1664-3224 (ISSN-L)
- PMC
- PMC6046629
- OpenAlex
- W2864895768
- Cited by
- 45
- References
- 44
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 10 · 2020: 9 · 2019: 7 · 2018: 2
- FWCI
- 5.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Immunology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Eli Lilly and Company
- Hermann und Lilly Schilling-Stiftung für Medizinische Forschung
- Deutsche Forschungsgemeinschaft (SFB 1192, RA 2893/2, SFB 841, 310/11)
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- ADP-ribosylation, NAD+, tissue-resident memory T cells, liver, Listeria monocytogenes infection, cell isolation, KLRG1, CD69, CD4+ T cells, CD8+ T cells, cytokine profiling
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