scholarly journals Regulation of Gene Expression in Autoimmune Disease Loci and the Genetic Basis of Proliferation in CD4+ Effector Memory T Cells

PLoS Genetics ◽  
2014 ◽  
Vol 10 (6) ◽  
pp. e1004404 ◽  
Author(s):  
Xinli Hu ◽  
Hyun Kim ◽  
Towfique Raj ◽  
Patrick J. Brennan ◽  
Gosia Trynka ◽  
...  
Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 1952-1960 ◽  
Author(s):  
Chang H. Kim ◽  
Hyung W. Lim ◽  
Jong R. Kim ◽  
Lusijah Rott ◽  
Peter Hillsamer ◽  
...  

Abstract Gene expression profiling was used to compare the gene expression patterns of human germinal center (GC) T helper (Th) cells with other CD4+ T-cell subsets (naive, central, and effector memory T cells). GC-Th cells, specifically localized in germinal centers to help B cells, are distantly related to central and effector memory T cells in global gene expression profiles. GC-Th cells displayed substantial differences in mRNA for adhesion molecules, chemoattractant receptors, and cytokines compared with other populations. Distinct expression of transcriptional factors by GC-Th cells is consistent with the hypothesis that they may be different from other T cells in cell lineage. Interestingly, CXCL13, a critical chemokine for B-cell entry to lymphoid follicles, is one of the most highly up-regulated genes in GC-Th cells. GC-Th cells (but not other T cells) produce and secrete large amounts of functional CXCL13 upon T-cell receptor activation, a process that is dependent on costimulation, requires translation and transcription, and is dramatically enhanced by activation in the presence of GC-B cells. This study revealed for the first time the unique gene expression program of GC-Th cells.


2019 ◽  
Vol 4 (40) ◽  
pp. eaaw2707 ◽  
Author(s):  
Masahiko Akamatsu ◽  
Norihisa Mikami ◽  
Naganari Ohkura ◽  
Ryoji Kawakami ◽  
Yohko Kitagawa ◽  
...  

A promising way to restrain hazardous immune responses, such as autoimmune disease and allergy, is to convert disease-mediating T cells into immunosuppressive regulatory T (Treg) cells. Here, we show that chemical inhibition of the cyclin-dependent kinase 8 (CDK8) and CDK19, or knockdown/knockout of the CDK8 or CDK19 gene, is able to induce Foxp3, a key transcription factor controlling Treg cell function, in antigen-stimulated effector/memory as well as naïve CD4+ and CD8+ T cells. The induction was associated with STAT5 activation, independent of TGF-β action, and not affected by inflammatory cytokines. Furthermore, in vivo administration of a newly developed CDK8/19 inhibitor along with antigen immunization generated functionally stable antigen-specific Foxp3+ Treg cells, which effectively suppressed skin contact hypersensitivity and autoimmune disease in animal models. The results indicate that CDK8/19 is physiologically repressing Foxp3 expression in activated conventional T cells and that its pharmacological inhibition enables conversion of antigen-specific effector/memory T cells into Foxp3+ Treg cells for the treatment of various immunological diseases.


2017 ◽  
Vol 8 ◽  
Author(s):  
Luca Pangrazzi ◽  
Erin Naismith ◽  
Andreas Meryk ◽  
Michael Keller ◽  
Brigitte Jenewein ◽  
...  

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