Contraction of intestinal effector T cells by retinoic acid-induced purinergic receptor P2X7

Hashimoto-Hill, Seika; Friesen, Leon; Kim, M; Kim, C H

doi:10.1038/mi.2016.109

Cited by 49 publications

(64 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Within intron 2 of P2rx7, an enhancer was revealed by enrichment of H3K4me1 (Fig. 3A), which is consistent with previous reports (32). The combination of H3K27ac and H3K4me1 marks identifies active enhancers (30); however, the P2rx7 enhancer lacked H3K27ac (Fig.…”

Section: Hdac3-deficient Dp Thymocytes Are Susceptible To P2x7 Receptsupporting

confidence: 91%

Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor–Induced Cell Death

Philips

McCue

Rajcula

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

Intricate life-versus-death decisions are programmed during T cell development, and the regulatory mechanisms that coordinate their activation and repression are still under investigation. In this study, HDAC3-deficient double-positive (DP) thymocytes exhibit a severe decrease in numbers. The thymic cortex is rich in ATP, which is released by macrophages that clear apoptotic DP thymocytes that fail to undergo positive selection. We demonstrate that HDAC3 is required to repress expression of the purinergic receptor P2X7 to prevent DP cell death. HDAC3-deficient DP thymocytes upregulate the P2X7 receptor, increasing sensitivity to ATP-induced cell death. P2rx7/HDAC3-double knockout mice show a partial rescue in DP cell number. HDAC3 directly binds to the P2rx7 enhancer, which is hyperacetylated in the absence of HDAC3. In addition, RORgt binds to the P2rx7 enhancer and promotes P2X7 receptor expression in the absence of HDAC3. Therefore, HDAC3 is a critical regulator of DP thymocyte survival and is required to suppress P2X7 receptor expression.

show abstract

Section: Hdac3-deficient Dp Thymocytes Are Susceptible To P2x7 Receptsupporting

confidence: 91%

Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor–Induced Cell Death

Philips

McCue

Rajcula

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…D). This is in accordance with reports showing that P2X7 expression is sensitive to retinoic acid, a vitamin A metabolite produced by intestinal dendritic cells . These results would suggest a different sensitivity to ART2.2/P2X7‐mediated cell death depending on both, the CD4 T cell subset looked at and the origin of the material (as shown for intestinal CD8 T cells ).…”

supporting

confidence: 92%

Blocking the ART2.2/P2X7‐system is essential to avoid a detrimental bias in functional CD4 T cell studies

et al. 2018

View full text Add to dashboard Cite

show abstract

“…This might be due to the environmental cues present only in periphery. Retinoic acid reportedly induces P2RX7 expression in intestinal lymphocytes (41), being a potential factor that influences the expression of ARTC2.2 and P2RX7 in iNKT and CD8 + T cells residing in nonlymphoid tissues. Whether retinoic acid itself or similar molecules drive expression in other tissues is still unknown and will certainly be a subject of future studies.…”

Section: Discussionmentioning

confidence: 99%

ARTC2.2/P2RX7 Signaling during Cell Isolation Distorts Function and Quantification of Tissue-Resident CD8+ T Cell and Invariant NKT Subsets

Silva

Wang

Qian

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

Peripheral invariant NKT cells (iNKT) and CD8+ tissue-resident memory T cells (TRM) express high levels of the extracellular ATP receptor P2RX7 in mice. High extracellular ATP concentrations or NAD-mediated P2RX7 ribosylation by the enzyme ARTC2.2 can induce P2RX7 pore formation and cell death. Because both ATP and NAD are released during tissue preparation for analysis, cell death through these pathways may compromise the analysis of iNKT and CD8+ TRM. Indeed, ARTC2.2 blockade enhanced recovery of viable liver iNKT and TRM. The expression of ARTC2.2 and P2RX7 on distinct iNKT subsets and TRM is unclear, however, as is the impact of recovery from other nonlymphoid sites. In this study, we performed a comprehensive analysis of ARTC2.2 and P2RX7 expression in iNKT and CD8+ T cells in diverse tissues, at steady-state and after viral infection. NKT1 cells and CD8+ TRM express high levels of both ARTC2.2 and P2RX7 compared with NKT2, NKT17, and CD8+ circulating memory subsets. Using nanobody-mediated ARTC2.2 antagonism, we showed that ARTC2.2 blockade enhanced NKT1 and TRM recovery from nonlymphoid tissues during cell preparation. Moreover, blockade of this pathway was essential to preserve functionality, viability, and proliferation of both populations. We also showed that short-term direct P2RX7 blockade enhanced recovery of TRM, although to a lesser degree. In summary, our data show that short-term in vivo blockade of the ARTC2.2/P2RX7 axis permits much improved flow cytometry–based phenotyping and enumeration of murine iNKT and TRM from nonlymphoid tissues, and it represents a crucial step for functional studies of these populations.

show abstract

Contraction of intestinal effector T cells by retinoic acid-induced purinergic receptor P2X7

Cited by 49 publications

References 44 publications

Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor–Induced Cell Death

Cutting Edge: HDAC3 Protects Double-Positive Thymocytes from P2X7 Receptor–Induced Cell Death

Blocking the ART2.2/P2X7‐system is essential to avoid a detrimental bias in functional CD4 T cell studies

ARTC2.2/P2RX7 Signaling during Cell Isolation Distorts Function and Quantification of Tissue-Resident CD8+ T Cell and Invariant NKT Subsets

Contact Info

Product

Resources

About