The chromosome 15q14 locus for bipolar disorder and schizophrenia: Is C15orf53 a major candidate gene?

Kranz, Thorsten M.; Ekawardhani, Savira; Lin, Michelle K.; Witzmann, Simone R.; Streit, Fabian; Bauer, Hans; Henseler, Darja; Turner, Jonathan D.; Reif, Andreas; Schote, Andrea B.; Meyer, Jobst

doi:10.1016/j.jpsychires.2012.08.008

Cited by 4 publications

(1 citation statement)

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“…Of note, c15orf53, a gene associated with mental disorder, showed strong connections to the suppression of Teff cell genes (six interactions). This gene is highly expressed in human CD4 + T cells and in the human limbic brain (39), and its high expression in Treg cells (FC = 5.82) suggests a potential role in regulating the Teff cell genes. It is important to note that our network analysis did not pick up genes whose expression was relatively constant across Treg cell subsets such as FOXP3.…”

Section: Interactions Between Treg Cell and Teff Cell Genesmentioning

confidence: 99%

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Hua

Davis

Hill

et al. 2015

The Journal of Immunology

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Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses. In this study, we analyzed human Treg cell subpopulations in the peripheral blood by performing genome-wide expression profiling of 40 Treg cell subsets from healthy donors. We found that the human peripheral blood Treg cell population is comprised of five major genomic subgroups, represented by 16 tractable subsets with a particular cell surface phenotype. These subsets possess a range of suppressive function and cytokine secretion and can exert a genomic footprint on target effector T (Teff) cells. Correlation analysis of variability in gene expression in the subsets identified several cell surface molecules associated with Treg suppressive function, and pharmacological interrogation revealed a set of genes having causative effect. The five genomic subgroups of Treg cells imposed a preserved pattern of gene expression on Teff cells, with a varying degree of genes being suppressed or induced. Notably, there was a cluster of genes induced by Treg cells that bolstered an autoinhibitory effect in Teff cells, and this induction appears to be governed by a different set of genes than ones involved in counteracting Teff activation. Our work shows an example of exploiting the diversity within human Treg cell subpopulations to dissect Treg cell biology.

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Section: Interactions Between Treg Cell and Teff Cell Genesmentioning

confidence: 99%