Erratum: Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours

Milner, J. Justin; Toma, Clara; Yu, Bingfei; Zhang, Kai; Omilusik, Kyla; Phan, Anthony T.; Wei, Dapeng; Getzler, Adam J.; Nguyen, Toan; Crotty, Shane; Wang, Wei; Pipkin, Matthew E.; Goldrath, Ananda W.

doi:10.1038/nature25445

Cited by 9 publications

(7 citation statements)

References 1 publication

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“…Finally, since a previous study demonstrated an essential role of Runx3 for promoting memory cell formation ( 18 , 46 ), we investigated the impact of MAZR- and/or Runx3-deletion on the generation of memory precursor (MP) CTLs. For this, we examined KLRG1 and CD127 expression patterns of the mutant CTLs, which allows us to identify KLRG1 – CD127 + MP and KLRG1 + CD127 – terminal effector (TE) CTLs ( 5 , 8 , 10 ).…”

Section: Resultsmentioning

confidence: 99%

Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells

Gülich

Rica²,

Tizian³

et al. 2021

Front. Immunol.

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The BTB zinc finger transcription factor MAZR (also known as PATZ1) controls, partially in synergy with the transcription factor Runx3, the development of CD8 lineage T cells. Here we explored the role of MAZR as well as combined activities of MAZR/Runx3 during cytotoxic T lymphocyte (CTL) and memory CD8+ T cell differentiation. In contrast to the essential role of Runx3 for CTL effector function, the deletion of MAZR had a mild effect on the generation of CTLs in vitro. However, a transcriptome analysis demonstrated that the combined deletion of MAZR and Runx3 resulted in much more widespread downregulation of CTL signature genes compared to single Runx3 deletion, indicating that MAZR partially compensates for loss of Runx3 in CTLs. Moreover, in line with the findings made in vitro, the analysis of CTL responses to LCMV infection revealed that MAZR and Runx3 cooperatively regulate the expression of CD8α, Granzyme B and perforin in vivo. Interestingly, while memory T cell differentiation is severely impaired in Runx3-deficient mice, the deletion of MAZR leads to an enlargement of the long-lived memory subset and also partially restored the differentiation defect caused by loss of Runx3. This indicates distinct functions of MAZR and Runx3 in the generation of memory T cell subsets, which is in contrast to their cooperative roles in CTLs. Together, our study demonstrates complex interplay between MAZR and Runx3 during CTL and memory T cell differentiation, and provides further insight into the molecular mechanisms underlying the establishment of CTL and memory T cell pools.

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Section: Resultsmentioning

confidence: 99%

Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells

Gülich

Rica²,

Tizian³

et al. 2021

Front. Immunol.

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“…In contrast, the 21 postnatal-specific TFs are associated with specialized functions, such as immune system development, response to stress, and response to the chemical. For example, RUNX3 plays important roles in the B-cell proliferation ( 26 , 27 ) and T-cell development ( 28 ).…”

Section: Resultsmentioning

confidence: 99%

Taiji-reprogram: a framework to uncover cell-type specific regulators and predict cellular reprogramming cocktails

Wang

Liu

Chen

et al. 2021

NAR Genomics and Bioinformatics

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Cellular reprogramming is a promising technology to develop disease models and cell-based therapies. Identification of the key regulators defining the cell type specificity is pivotal to devising reprogramming cocktails for successful cell conversion but remains a great challenge. Here, we present a systems biology approach called Taiji-reprogram to efficiently uncover transcription factor (TF) combinations for conversion between 154 diverse cell types or tissues. This method integrates the transcriptomic and epigenomic data to construct cell-type specific genetic networks and assess the global importance of TFs in the network. Comparative analysis across cell types revealed TFs that are specifically important in a particular cell type and often tightly associated with cell-type specific functions. A systematic search of TFs with differential importance in the source and target cell types uncovered TF combinations for desired cell conversion. We have shown that Taiji-reprogram outperformed the existing methods to better recover the TFs in the experimentally validated reprogramming cocktails. This work not only provides a comprehensive catalog of TFs defining cell specialization but also suggests TF combinations for direct cell conversion.

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“…The DEGseq was used to analyze the differentially expressed genes. To confirm the characteristics of induced T RM , we compared the T RM -related genes previously reported in various mouse models (24)(25)(26)(27)(28)(29). The result showed that the expressions of Itgae, Cd69, Nr4a1 (Nur77), Nr4a2, Ctla4, Cdh1, Cd244, Prdm1, Rgs, Fabp5, and Bhlhe40 are up-regulated, and S1pr1, Ccr7, Sell, and Hnf1a were down-regulated in induced CD8 + T RM (Fig.…”

Section: Long-lived Cd103 + Cd69 + T Rm Cells In Skin Induced By Allo...mentioning

confidence: 92%

Skin and heart allograft rejection solely by long-lived alloreactive T _RM cells in skin of severe combined immunodeficient mice

et al. 2022

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Whether induced tissue-resident memory T (T RM ) cells in nonlymphoid organs alone can mediate allograft rejection is unknown. By grafting alloskin or heart into severe combined immunodeficient or Rag2KO mice in which a piece of induced CD4 + and/or CD8 + T RM cell–containing MHC-matched or syngeneic skin was transplanted in advance, we addressed this issue. The induced CD4 + T RM cells in the skin alone acutely rejected alloskin or heart grafts. RNA-seq analysis showed that induced CD4 + T RM cells in skin favorably differentiated into T H 17-like polarization during the secondary immune response. Inhibition of the key T H 17 signaling molecule RORγt attenuated T RM cell–mediated graft rejection. Thus, we offer a unique mouse model to specifically study T RM cell–mediated allograft rejection without the involvement of lymphocytes in lymphoid organs and tissues. Our study provides strong evidence supporting the hypothesis that long-lived alloreactive T RM cells resident in other organs/tissues substantially contribute to organ allograft rejection.

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Erratum: Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours

Cited by 9 publications

References 1 publication

Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells

Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells

Taiji-reprogram: a framework to uncover cell-type specific regulators and predict cellular reprogramming cocktails

Skin and heart allograft rejection solely by long-lived alloreactive T _RM cells in skin of severe combined immunodeficient mice

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Erratum: Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours

Cited by 9 publications

References 1 publication

Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells

Complex Interplay Between MAZR and Runx3 Regulates the Generation of Cytotoxic T Lymphocyte and Memory T Cells

Taiji-reprogram: a framework to uncover cell-type specific regulators and predict cellular reprogramming cocktails

Skin and heart allograft rejection solely by long-lived alloreactive T RM cells in skin of severe combined immunodeficient mice

Contact Info

Product

Resources

About

Skin and heart allograft rejection solely by long-lived alloreactive T _RM cells in skin of severe combined immunodeficient mice