China
Africa
Explore chapters and articles related to this topic
Immunodeficiency Diseases
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Monogenic diseases affecting T regulatory cell biology, the role of T cell associated molecules and regulation of peripheral T cell tolerance are called Tregopathies (Cepka et al. 2018). They manifest with recurrent infections, autoimmunity and malignancy. In 2017 the International Union of Immunological Societies (IUIS) classified them as inborn errors of immunity. Each of these genes encode proteins that uniquely contribute to the function of thymus-derived forkhead box P3 (FOXP3) regulatory T cells or Tregs. They are caused by Loss-Of-Function (LOF) mutations in FOXP3, cytotoxic T lymphocyte-associated antigen 4 (CTLA4), LPS- Responsive and Beige-like Anchor protein (LRBA), CD25, BTB domain and CNC homolog 2 (BACH2) and Gain Of Function (GOF) mutation in Signal Transducer and activator of Transcription 3 (STAT3). A description of the specific entity, the molecular defect and clinical phenotype/lab findings are depicted below in Table 29.14.
Tolerance and autoimmunity
Published in Gabriel Virella, Medical Immunology, 2019
George C. Tsokos, Gabriel Virella
Besides FOXP3, additional transcription factors are needed for the proper function and sustenance of Tregs. These include STAT5, the transcription regulator Bach2, and the chromatin remodeler special AT-rich sequence binding protein (SATB1).
Correlation of the transcription factors IRF4 and BACH2 with the abnormal NFATC1 expression in T cells from chronic myeloid leukemia patients
Published in Hematology, 2022
Yikai Zhang, Xiangbo Zeng, Xianfeng Zha, Jing Lai, Guangxiao Tan, Shaohua Chen, Xibao Yu, Yangqiu Li, Ling Xu
In addition, we found that BACH2, another transcription factor that potentially regulates NFATC1, was decreased in CML patient T cells. Although the PPI analysis result showed that there was no direct interaction between BACH2 and NFATC1, the RT-qPCR results in this study showed that BACH2 expression was positively correlated with NFATC1. One study has shown that up-regulating BACH2 can inhibit the program of terminal exhaustion molecules via transcriptional repression and epigenetic silencing [34]. These data suggested that down-regulation of BACH2 may be also related to T cell dysfunction in CML patients. Interestingly, our previous results have shown that the distribution of memory T cells in CML patients was skewed from naïve and central memory T cells to effector memory and effector T cells [52], in addition, we also found that there was an increased percentage of CD8+ T cell subset among the CD3+ T cell population in CML patients (Unpublished data). All of these alternations seem that the adaptive immune reaction was activated in CML patients, however, the current finding suggested that in the level of genetic, key transcription factors which response for activation, protective function, and inhibition of exhaustion of T cells were down-regulated. Further research needs to understand the clear molecular mechanisms behind these changes more deeply.
An overview of T follicular cells in transplantation: spotlight on their clinical significance
Published in Expert Review of Clinical Immunology, 2019
Qian Niu, Rens Kraaijeveld, Yi Li, Aleixandra Mendoza Rojas, Yunying Shi, Lanlan Wang, Nicole M Van Besouw, Carla C. Baan
The Tfh differentiation process is negatively regulated by Bcl-6 antagonists like the transcription factor Blimp-1. CD4+ T cells constitutively expressing Blimp-1 fail to acquire Tfh phenotype [29]. Importantly, the expression of Blimp-1 does not inhibit differentiation of other CD4+ helper lineages, indicating that Blimp-1 acts specifically on Bcl-6 [29]. In turn, Bcl-6 can also repress expression or activity of Blimp-1, as well as the T helper lineage-specific transcription factors T-bet, GATA3, and RORγt. Subsequently, the balance of these transcription factors determines the developmental fate of Tfh and non-Tfh helper cells. Recently, Geng et al. [41] identified that the transcription factor Bach2 is a negative regulator of Tfh cell differentiation, through negative regulation of CXCR5 expression. In addition to transcription factors, cytokines also control the expression of Bcl-6; an example is IL-2, which suppresses this factor via STAT5 and subsequent induction of Blimp-1 [42]. Besides, PD-1 also has an inhibitory role in Tfh cell differentiation [17]. It is clear that our knowledge about the modulation of Tfh cell differentiation is incomplete.
Association of increased eomesodermin, BCL6, and granzyme B expression with major clinical manifestations of Hashimoto’s thyroiditis – an observational study
Published in Immunological Investigations, 2018
Mario Štefanić, Stana Tokić, Mirjana Suver Stević, Ljubica Glavaš-Obrovac
Several transcription factors have been implicated in programming the CTL functions (Crotty et al., 2010; Hu and Chen, 2013). Of these, major regulators include a T-box transcription factor (TF) eomesodermin (EOMES), B cell CLL/lymphoma 6 (BCL6), and transcription factor 1 (TCF1, encoded by TCF7), which coordinate effector to memory differentiation of T cells (Crotty et al., 2010; Hu and Chen, 2013; Pearce et al., 2003). By contrast, BTB and CNC homology 2 (BACH2) is a key negative regulator of terminal effector differentiation in conventional T cell lineages (Hu and Chen, 2013). Genetic ablation of BACH2 results in the reduction of CD8+ central memory and CD4+FoxP3+Treg cells, with a concomitant increase in short-lived effector cells and CD4+Th cells, respectively (Roychoudhuri et al., 2016, 2013). EOMES expression is also central to the cytotoxic transdifferentiation of CD4+Th cells and renders CD4+ and CD8+T cells pathogenic by activating granzyme B (GZMB), PRF, and FasL pathways (Eshima et al., 2012). GZMB, an effector serine protease that activates target cell apoptosis through caspase-dependent and independent pathways, is regularly expressed by activated CTL and belongs to cytotoxicity-associated transcripts often used as indicators of CTL presence in tissues (Pearce et al., 2003).