Janus Kinases and STAT Family Transcription Factors: Their Role in the Function and Development of Lymphoid Cells

2003 ◽  
pp. 229-254
Author(s):  
Tammy P. Cheng ◽  
Jérôme Galon ◽  
Roberta Visconti ◽  
Massimo Gadina ◽  
John J. O'Shea
Keyword(s):  
Transcription Factors ◽  
Lymphoid Cells ◽  
Janus Kinases

scholarly journals Transcription Factors in the Development and Function of Group 2 Innate Lymphoid Cells

2019 ◽  
Vol 20 (6) ◽  
pp. 1377 ◽  
Author(s):  
Takashi Ebihara ◽  
Ichiro Taniuchi
Keyword(s):  
Transcription Factors ◽  
Physiological State ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Th2 Cytokine ◽  
Parasitic Worm ◽  
Group 2 ◽  
And Function

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells and are a major source of innate TH2 cytokine secretion upon allergen exposure or parasitic-worm infection. Accumulating studies have revealed that transcription factors, including GATA-3, Bcl11b, Gfi1, RORα, and Ets-1, play a role in ILC2 differentiation. Recent reports have further revealed that the characteristics and functions of ILC2 are influenced by the physiological state of the tissues. Specifically, the type of inflammation strongly affects the ILC2 phenotype in tissues. Inhibitory ILC2s, memory-like ILC2s, and ex-ILC2s with ILC1 features acquire their characteristic properties following exposure to their specific inflammatory environment. We have recently reported a new ILC2 population, designated as exhausted-like ILC2s, which emerges after a severe allergic inflammation. Exhausted-like ILC2s are featured with low reactivity and high expression of inhibitory receptors. Therefore, for a more comprehensive understanding of ILC2 function and differentiation, we review the recent knowledge of transcriptional regulation of ILC2 differentiation and discuss the roles of the Runx transcription factor in controlling the emergence of exhausted-like ILC2s. The concept of exhausted-like ILC2s sheds a light on a new aspect of ILC2 biology in allergic diseases.

Characterization of interactions between transcription factors and a regulatory region spanning nt −320 to −281 of the HIV-1 LTR in T-lymphoid and non-T-lymphoid cells

2002 ◽  
Vol 9 (1) ◽  
pp. 68-81
Author(s):  
Lloyd A. Pereira ◽  
Melissa J. Churchill ◽  
Andrew G. Elefanty ◽  
Theo Gouskos ◽  
Paul F. Lambert ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Regulatory Region ◽  
Lymphoid Cells ◽  
Hiv 1

scholarly journals Interleukin 7 Receptor Control of  T Cell Receptor γ Gene Rearrangement: Role of Receptor-associated Chains and Locus Accessibility

1998 ◽  
Vol 188 (12) ◽  
pp. 2233-2241 ◽  
Author(s):  
Scott K. Durum ◽  
Serge Candèias ◽  
Hiroshi Nakajima ◽  
Warren J. Leonard ◽  
Allison M. Baird ◽  
...  
Keyword(s):  
Transcription Factors ◽  
T Cell ◽  
T Cell Receptor ◽  
Dna Cleavage ◽  
Gene Rearrangement ◽  
Trichostatin A ◽  
Cell Receptor ◽  
Lymphoid Cells ◽  
Janus Kinase ◽  
Interleukin 7

VDJ recombination of T cell receptor and immunoglobulin loci occurs in immature lymphoid cells. Although the molecular mechanisms of DNA cleavage and ligation have become more clear, it is not understood what controls which target loci undergo rearrangement. In interleukin 7 receptor (IL-7R)α−/− murine thymocytes, it has been shown that rearrangement of the T cell receptor (TCR)-γ locus is virtually abrogated, whereas other rearranging loci are less severely affected. By examining different strains of mice with targeted mutations, we now observe that the signaling pathway leading from IL-7Rα to rearrangement of the TCR-γ locus requires the γc receptor chain and the γc-associated Janus kinase Jak3. Production of sterile transcripts from the TCR-γ locus, a process that generally precedes rearrangement of a locus, was greatly repressed in IL-7Rα−/− thymocytes. The repressed transcription was not due to a lack in transcription factors since the three transcription factors known to regulate this locus were readily detected in IL-7Rα−/− thymocytes. Instead, the TCR-γ locus was shown to be methylated in IL-7Rα−/− thymocytes. Treatment of IL-7Rα−/− precursor T cells with the specific histone deacetylase inhibitor trichostatin A released the block of TCR-γ gene rearrangement. This data supports the model that IL-7R promotes TCR-γ gene rearrangement by regulating accessibility of the locus via demethylation and histone acetylation of the locus.

scholarly journals T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

2020 ◽  
Author(s):  
J-H Schroeder ◽  
N Garrido-Mesa ◽  
T Zabinski ◽  
AL Gallagher ◽  
L Campbell ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Fate Mapping ◽  
Functional Roles ◽  
Mucosal Surfaces ◽  
Group 2

ABSTRACTInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are “fate-mapped” for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces.SUMMARYInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.

Regulating the development of pulmonary Group 2 innate lymphoid cells

2019 ◽  
Vol 400 (11) ◽  
pp. 1497-1507 ◽  
Author(s):  
Sofia Helfrich ◽  
Claudia U. Duerr
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Morphological Changes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
The Family ◽  
Intrinsic Regulation ◽  
Group 2 ◽  
And Function

Abstract Group 2 innate lymphoid cells (ILC2s) are members of the family of innate lymphoid cells and are innately committed to type 2 immune responses. In the lungs, ILC2s are the predominant population of innate lymphoid cells (ILCs) and their development is orchestrated by several different transcription factors ensuring lineage commitment by intrinsic regulation. ILC2s are present in the lungs from the foetal period onwards and are thus exposed to extrinsic regulation due to the airways’ continuous morphological changes upon birth. In this review, we will briefly summarise the dependence of ILC2s on transcription factors and discuss recently described characteristics and function of early life ILC2s in the lungs.

scholarly journals Dynamic balance between master transcription factors determines the fates and functions of CD4 T cell and innate lymphoid cell subsets

2017 ◽  
Vol 214 (7) ◽  
pp. 1861-1876 ◽  
Author(s):  
Difeng Fang ◽  
Jinfang Zhu
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
T Cell ◽  
Cd4 T Cells ◽  
T Regulatory Cells ◽  
Dynamic Balance ◽  
Treg Cells ◽  
Lymphoid Cells ◽  
Cd4 T Cell ◽  
Master Regulators

CD4 T cells, including T regulatory cells (Treg cells) and effector T helper cells (Th cells), and recently identified innate lymphoid cells (ILCs) play important roles in host defense and inflammation. Both CD4 T cells and ILCs can be classified into distinct lineages based on their functions and the expression of lineage-specific genes, including those encoding effector cytokines, cell surface markers, and key transcription factors. It was first recognized that each lineage expresses a specific master transcription factor and the expression of these factors is mutually exclusive because of cross-regulation among these factors. However, recent studies indicate that the master regulators are often coexpressed. Furthermore, the expression of master regulators can be dynamic and quantitative. In this review, we will first discuss similarities and differences between the development and functions of CD4 T cell and ILC subsets and then summarize recent literature on quantitative, dynamic, and cell type–specific balance between the master transcription factors in determining heterogeneity and plasticity of these subsets.

scholarly journals Shared Transcriptional Control of Innate Lymphoid Cell and Dendritic Cell Development

2019 ◽  
Vol 35 (1) ◽  
pp. 381-406 ◽  
Author(s):  
Prachi Bagadia ◽  
Xiao Huang ◽  
Tian-Tian Liu ◽  
Kenneth M. Murphy
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
T Cells ◽  
Dendritic Cells ◽  
Transcription Factors ◽  
Transcriptional Control ◽  
Lymphoid Cells ◽  
Transcriptional Networks ◽  
Innate Lymphoid Cell ◽  
Adaptive Immune

Innate immunity and adaptive immunity consist of highly specialized immune lineages that depend on transcription factors for both function and development. In this review, we dissect the similarities between two innate lineages, innate lymphoid cells (ILCs) and dendritic cells (DCs), and an adaptive immune lineage, T cells. ILCs, DCs, and T cells make up four functional immune modules and interact in concert to produce a specified immune response. These three immune lineages also share transcriptional networks governing the development of each lineage, and we discuss the similarities between ILCs and DCs in this review.

scholarly journals Deletion of genes encoding PU.1 and Spi-B leads to B cell acute lymphoblastic leukemia associated with driver mutations in Janus Kinases

2018 ◽  
Author(s):  
Carolina R. Batista ◽  
Michelle Lim ◽  
Anne-Sophie Laramée ◽  
Faisal Abu-Sardanah ◽  
Li S. Xu ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Amino Acid ◽  
Mouse Model ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Clonal Evolution ◽  
Driver Mutations ◽  
Janus Kinases ◽  
Cell Acute Lymphoblastic Leukemia

AbstractPrecursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with recurrent mutations that occur in cancer-initiating cells. There is a need to understand how spontaneous driver mutations influence clonal evolution in leukemia. The ETS-transcription factors PU.1 and Spi-B (encoded bySpi1andSpib) execute a critical role in B cell development and serve as complementary tumour suppressors by opposing the proliferative events mediated by IL-7R signaling. Here, we used a mouse model to conditionally deleteSpi1andSpibgenes in developing B cells. These mice developed B-ALL with a median time to euthanasia of 18 weeks. We performed RNA and whole-exome sequencing (WES) on leukemias isolated from Mb1-CreΔPB mice and identified single-nucleotide variants (SNVs) inJak1,Jak3andIkzf3genes, resulting in amino acid changes and in the gain of early stop-codons. JAK3 mutations resulted in amino acid substitutions located in the pseudo-kinase (R653H, V670A) and in the kinase (T844M) domains. Introduction of these mutations into wild-type pro-B cells conferred survival and proliferation advantages. We conclude that mutations in Janus kinases represent secondary drivers of leukemogenesis in the absence of Spi-B and PU.1 transcription factors. This mouse model represents an useful tool to study clonal evolution and tumour heterogeneity in B-ALL.

scholarly journals mTORC1 and mTORC2 differentially promote natural killer cell development

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Chao Yang ◽  
Shirng-Wern Tsaih ◽  
Angela Lemke ◽  
Michael J Flister ◽  
Monica S Thakar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Natural Killer Cell ◽  
Natural Killer ◽  
Nk Cell ◽  
Killer Cell ◽  
Cell Development ◽  
Lymphoid Cells ◽  
Innate And Adaptive Immunity ◽  
Mechanistic Target Of Rapamycin

Natural killer (NK) cells are innate lymphoid cells that are essential for innate and adaptive immunity. Mechanistic target of rapamycin (mTOR) is critical for NK cell development; however, the independent roles of mTORC1 or mTORC2 in regulating this process remain unknown. Ncr1iCre-mediated deletion of Rptor or Rictor in mice results in altered homeostatic NK cellularity and impaired development at distinct stages. The transition from the CD27+CD11b− to the CD27+CD11b+ stage is impaired in Rptor cKO mice, while, the terminal maturation from the CD27+CD11b+ to the CD27−CD11b+ stage is compromised in Rictor cKO mice. Mechanistically, Raptor-deficiency renders substantial alteration of the gene expression profile including transcription factors governing early NK cell development. Comparatively, loss of Rictor causes more restricted transcriptome changes. The reduced expression of T-bet correlates with the terminal maturation defects and results from impaired mTORC2-AktS473-FoxO1 signaling. Collectively, our results reveal the divergent roles of mTORC1 and mTORC2 in NK cell development.

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