MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production.
Immunity 44(4):821 (2016)
MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary ...
Targeting microRNAs for immunomodulation.
Current Opinion in Pharmacology 23:25 (2015)
microRNAs (miRNA) are small regulatory RNAs exerting pleiotropic functions in virtually any immune cell-type. Dozens of miRNAs with a known function in the immune system constitute interesting drug targets for immunomodulation. Chemical modifications of nucleic acid-based miRNA mimics and inhibi...
A subpopulation of CD103(pos) ICOS(pos) Treg cells occurs at high frequency in lymphopenic mice and represents a lymph node specific differentiation stage.
European Journal of Immunology 45(6):1760 (2015)
Regulatory T (Treg) cells are pivotal for the maintenance of peripheral tolerance by controlling self-reactive, chronic, and homeostatic T-cell responses. Here, we report that the increase in Treg-cell suppressive function observed in lymphopenic mice correlates with the degree of lymphopenia an...
Identification of MiR-205 As a MicroRNA That Is Highly Expressed in Medullary Thymic Epithelial Cells.
PLoS ONE 10(8):e0135440 (2015)
Thymic epithelial cells (TECs) support T cell development in the thymus. Cortical thymic epithelial cells (cTECs) facilitate positive selection of developing thymocytes whereas medullary thymic epithelial cells (mTECs) facilitate the deletion of self-reactive thymocytes in order to prevent autoi...
Canonical microRNAs in thymic epithelial cells promote central tolerance.
European Journal of Immunology 44(5):1313 (2014)
Medullary thymic epithelial cells (mTECs) facilitate the deletion of developing self-reactive T cells by displaying a diverse repertoire of tissue-specific antigens, a process which largely depends on the expression of the autoimmune regulator (Aire) gene. Mature microRNAs (miRNAs) that regulate...
microRNA-17-92 regulates IL-10 production by regulatory T cells and control of experimental autoimmune encephalomyelitis.
Journal of Immunology 191(4):1594 (2013)
microRNAs (miRNA) are essential for regulatory T cell (Treg) function but little is known about the functional relevance of individual miRNA loci. We identified the miR-17-92 cluster as CD28 costimulation dependent, suggesting that it may be key for Treg development and function. Although overal...
The microRNA cluster miR-17∼92 promotes TFH cell differentiation and represses subset-inappropriate gene expression.
Nature Immunology 14(8):840 (2013)
Follicular helper T cells (TFH cells) are the prototypic helper T cell subset specialized to enable B cells to form germinal centers (GCs) and produce high-affinity antibodies. We found that expression of microRNAs (miRNAs) by T cells was essential for TFH cell differentiation. More specifically...
MicroRNA regulation of T-cell differentiation and function.
Immunological Reviews 253(1):65 (2013)
MicroRNAs (miRNAs) are emerging as key controllers of T-cell differentiation and function. Their expression is dynamically regulated by extracellular signals such as costimulation and cytokine signals. miRNAs set thresholds for gene expression and optimize protein concentrations of genetic netwo...
DGCR8-mediated production of canonical microRNAs is critical for regulatory T cell function and stability.
PLoS ONE 8(5):e66282 (2013)
Regulatory T cells (Treg) are integral for immune homeostasis. Here we demonstrate that canonical microRNAs (miRNAs) are required for Treg function because mice with DGCR8-deficient Treg cells spontaneously develop a scurfy-like disease. Using genetic lineage marking we show that absence of miRN...
A resource for the conditional ablation of microRNAs in the mouse.
Cell Reports 1(4):385 (2012)
The importance of miRNAs during development and disease processes is well established. However, most studies have been done in cells or with patient tissues, and therefore the physiological roles of miRNAs are not well understood. To unravel in vivo functions of miRNAs, we have generated conditi...
Breakdown in peripheral tolerance in type 1 diabetes in mice and humans.
Cold Spring Harbor perspectives in medicine 2(3):a007807 (2012)
Type 1 Diabetes (T1D), also called juvenile diabetes because of its classically early onset, is considered an autoimmune disease targeting the insulin-producing β cells in the pancreatic islets of Langerhans. T1D reflects a loss of tolerance to tissue self-antigens caused by defects in both cent...
MicroRNA 10a marks regulatory T cells.
PLoS ONE 7(5):e36684 (2012)
MicroRNAs (miRNAs) are crucial for regulatory T cell (Treg) stability and function. We report that microRNA-10a (miR-10a) is expressed in Tregs but not in other T cells including individual thymocyte subsets. Expression profiling in inbred mouse strains demonstrated that non-obese diabetic (NOD)...
Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development.
Journal of Experimental Medicine 208(2):383 (2011)
Dendritic cells (DCs) in the thymus (tDCs) are predominantly accumulated in the medulla and contribute to the establishment of self-tolerance. However, how the medullary accumulation of tDCs is regulated and involved in self-tolerance is unclear. We show that the chemokine receptor XCR1 is expre...
Small RNA regulators of T cell-mediated autoimmunity.
Journal of Clinical Immunology 30(3):347 (2010)
MicroRNAs (miRNAs) are short singlestranded RNA molecules that regulate gene expression post-transcriptionally. Several hundred miRNAs exist in the mammalian genome and regulate developmental processes, cell cycle, and survival.
In this review,we highlight generalmodes of miRNA function and rela...
Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo.
Nature Immunology 10(9):1000 (2009)
Regulatory T cells (T(reg) cells) are central to the maintenance of immune homeostasis. However, little is known about the stability of T(reg) cells in vivo. In this study, we demonstrate that a substantial percentage of cells had transient or unstable expression of the transcription factor Foxp...
Plasticity of CD4(+) FoxP3(+) T cells.
Current Opinion in Immunology 21(3):281 (2009)
Regulatory T (Treg) cells play an essential role in maintaining immunological tolerance. The discovery of FoxP3 as a key Treg transcription factor combined with recent advances in the development of functional reporter mice has enabled new insights into Treg biology and revealed unexpected featu...
Stabilized beta-catenin in thymic epithelial cells blocks thymus development and function.
Journal of Immunology 182(5):2997 (2009)
Thymic T cell development is dependent on a specialized epithelial microenvironment mainly composed of cortical and medullary thymic epithelial cells (TECs). The molecular programs governing the differentiation and maintenance of TECs remain largely unknown. Wnt signaling is central to the devel...
Maintenance of a normal thymic microenvironment and T-cell homeostasis require Smad4-mediated signaling in thymic epithelial cells.
Blood 112(9):3688 (2008)
Signals mediated by the transforming growth factor-beta superfamily of growth factors have been implicated in thymic epithelial cell (TEC) differentiation, homeostasis, and function, but a direct reliance on these signals has not been established. Here we demonstrate that a block in canonical tr...
Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity.
Journal of Experimental Medicine 205(9):1983 (2008)
A new regulatory T (T reg) cell-specific, FoxP3-GFP-hCre bacterial artificial chromosome transgenic mouse was crossed to a conditional Dicer knockout (KO) mouse strain to analyze the role of microRNAs (miRNAs) in the development and function of T reg cells. Although thymic T reg cells developed ...
TGF-beta signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution.
Blood 112(3):626 (2008)
The thymus constitutes the primary lymphoid organ responsible for the generation of naive T cells. Its stromal compartment is largely composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection...