Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development

Morgan, Roxroy C; Kee, Barbara L.

doi:10.4049/jimmunol.2200141

Cited by 9 publications

(6 citation statements)

References 132 publications

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“…To this end, one might need to isolate DNA/RNA and protein for downstream applications such as real-time PCR to evaluate expression of specific genes (Gioulbasani et al, 2020;Pereira et al, 2014) or to perform multiomic analysis such as RNA-seq to evaluate gene expression, ATAC-seq to evaluate chromatin accessibility, whole-genome bisulfite sequencing to assess DNA methylation, or CMS-IP sequencing to assess distribution of 5-hydroxymethylcytosine (Aijo et al, 2022;Engel et al, 2016;Theofilatos et al, 2022;Tsagaratou et al, 2017). Collectively, the past few years' integrative analyses of multiomic approaches have shed light on the transcriptional and epigenetic regulation of iNKT cells (Morgan & Kee, 2022). For the above experiments, it is critical to identify iNKT cell subsets while maintaining the cells alive.…”

Section: Identifying Inkt Cell Subsets Based On Surface Marker Expres...mentioning

confidence: 99%

“…It is critical to focus on specific subsets in order to decipher the unique features that define them. Research in the last decade has shed light on distinct transcriptional and epigenetic principles that govern the development of each subset (Harsha Krovi et al., 2020; Morgan & Kee, 2022; Verykokakis & Kee, 2018). iNKT subsets are transcriptionally and epigenetically heterogeneous, with varying regulation leading to their distinct effector functions (Engel et al., 2016).…”

Section: Commentarymentioning

confidence: 99%

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Defining iNKT Cell Subsets and Their Function by Flow Cytometry

Gioulbasani

Tsagaratou

2023

Current Protocols

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This article discusses methods to assess invariant natural killer T (iNKT) cell subsets isolated from the thymus, as well as the spleen, the liver, and the lung. iNKT cells can be subdivided in distinct, functional subsets based on the transcription factors they express and the cytokines they produce to regulate the immune response. Basic Protocol 1 focuses on characterizing murine iNKT subsets ex vivo by flow cytometry by evaluating the expression of lineagespecifying transcription factors such as PLZF and RORγt. The Alternate Protocol describes a detailed approach to define subsets based on expression of surface markers. This approach can be very useful for maintaining the subsets alive, without fixing them, in order to isolate them for downstream molecular assays such as DNA/RNA isolation, genome-wide analysis to assess gene expression (such as RNA-seq), assessment of chromatin accessibility (for instance, by ATAC-seq), and assessment of DNA methylation by whole-genome bisulfite sequencing. Basic Protocol 2 describes the functional characterization of iNKT cells, which are activated in vitro with PMA and ionomycin for a short period of time and subsequently stained and characterized for production of cytokines, such as IFNγ and IL-4, by flow cytometry. Basic Protocol 3 describes the process of activating iNKT cells in vivo using α-galactosyl-ceramide, a lipid that can be recognized specifically by iNKT cells, allowing assessment of their functionality in vivo. Cells are then isolated and directly stained for cytokine secretion.

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Section: Identifying Inkt Cell Subsets Based On Surface Marker Expres...mentioning

confidence: 99%

Section: Commentarymentioning

confidence: 99%

Defining iNKT Cell Subsets and Their Function by Flow Cytometry

Gioulbasani

Tsagaratou

2023

Current Protocols

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“…This specific binding towards DNA sequences could inhibit transcription by recruiting co-repressors via its amino terminal POZ domain. However, PLZF is also able to stimulate transcription depending on the activator and suppressor [35,93]. According to previous studies, PLZF was found to be involved in diverse signaling as well as differentiation and growth-regulatory pathways [58].…”

Section: Plzfmentioning

confidence: 99%

The Role of Promyelocytic Leukemia Zinc Finger (PLZF) and Glial-Derived Neurotrophic Factor Family Receptor Alpha 1 (GFRα1) in the Cryopreservation of Spermatogonia Stem Cells

Shamhari

Jefferi

Hamid

et al. 2023

IJMS

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The cryopreservation of spermatogonia stem cells (SSCs) has been widely used as an alternative treatment for infertility. However, cryopreservation itself induces cryoinjury due to oxidative and osmotic stress, leading to reduction in the survival rate and functionality of SSCs. Glial-derived neurotrophic factor family receptor alpha 1 (GFRα1) and promyelocytic leukemia zinc finger (PLZF) are expressed during the self-renewal and differentiation of SSCs, making them key tools for identifying the functionality of SSCs. To the best of our knowledge, the involvement of GFRα1 and PLZF in determining the functionality of SSCs after cryopreservation with therapeutic intervention is limited. Therefore, the purpose of this review is to determine the role of GFRα1 and PLZF as biomarkers for evaluating the functionality of SSCs in cryopreservation with therapeutic intervention. Therapeutic intervention, such as the use of antioxidants, and enhancement in cryopreservation protocols, such as cell encapsulation, cryoprotectant agents (CPA), and equilibrium of time and temperature increase the expression of GFRα1 and PLZF, resulting in maintaining the functionality of SSCs. In conclusion, GFRα1 and PLZF have the potential as biomarkers in cryopreservation with therapeutic intervention of SSCs to ensure the functionality of the stem cells.

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“…Innate/innate-like effector lymphocytes are quick responders; they can act as quickly as cells of innate immune system or faster [reviewed in refs ( 21 , 22 )]. This feature in several innate/innate-like effector lymphocytes is ingrained during development by a genome regulatory network under the control of a promyelocytic leukemia zinc finger transcription factor (encoded by Zbtb16 ; reviewed in ref ( 35 , 36 )]. Activated innate/innate-like effector lymphocytes secrete a wide variety of cytokines and chemokines with which they can steer downstream type I, II, and III immune responses ( Figure 2 ).…”

Section: Introduction: ‘For a Secret Offence A Secret Revenge’mentioning

confidence: 99%

Die Kämpfe únd schláchten—the struggles and battles of innate-like effector T lymphocytes with microbes

2023

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The large majority of lymphocytes belong to the adaptive immune system, which are made up of B2 B cells and the αβ T cells; these are the effectors in an adaptive immune response. A multitudinous group of lymphoid lineage cells does not fit the conventional lymphocyte paradigm; it is the unconventional lymphocytes. Unconventional lymphocytes—here called innate/innate-like lymphocytes, include those that express rearranged antigen receptor genes and those that do not. Even though the innate/innate-like lymphocytes express rearranged, adaptive antigen-specific receptors, they behave like innate immune cells, which allows them to integrate sensory signals from the innate immune system and relay that umwelt to downstream innate and adaptive effector responses. Here, we review natural killer T cells and mucosal-associated invariant T cells—two prototypic innate-like T lymphocytes, which sense their local environment and relay that umwelt to downstream innate and adaptive effector cells to actuate an appropriate host response that confers immunity to infectious agents.

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Genomic and Transcriptional Mechanisms Governing Innate-like T Lymphocyte Development

Cited by 9 publications

References 132 publications

Defining iNKT Cell Subsets and Their Function by Flow Cytometry

Defining iNKT Cell Subsets and Their Function by Flow Cytometry

The Role of Promyelocytic Leukemia Zinc Finger (PLZF) and Glial-Derived Neurotrophic Factor Family Receptor Alpha 1 (GFRα1) in the Cryopreservation of Spermatogonia Stem Cells

Die Kämpfe únd schláchten—the struggles and battles of innate-like effector T lymphocytes with microbes

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