The RNAseIII enzyme Drosha is critical in T cells for preventing lethal inflammatory disease
Open Access
- 25 August 2008
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 205 (9) , 2005-2017
- https://doi.org/10.1084/jem.20081219
Abstract
MicroRNAs (miRNAs) are implicated in the differentiation and function of many cell types. We provide genetic and in vivo evidence that the two RNaseIII enzymes, Drosha and Dicer, do indeed function in the same pathway. These have previously been shown to mediate the stepwise maturation of miRNAs (Lee, Y., C. Ahn, J. Han, H. Choi, J. Kim, J. Yim, J. Lee, P. Provost, O. Radmark, S. Kim, and V.N. Kim. 2003. Nature. 425:415–419), and genetic ablation of either within the T cell compartment, or specifically within Foxp3+ regulatory T (T reg) cells, results in identical phenotypes. We found that miRNA biogenesis is indispensable for the function of T reg cells. Specific deletion of either Drosha or Dicer phenocopies mice lacking a functional Foxp3 gene or Foxp3+ cells, whereas deletion throughout the T cell compartment also results in spontaneous inflammatory disease, but later in life. Thus, miRNA-dependent regulation is critical for preventing spontaneous inflammation and autoimmunity.Keywords
This publication has 45 references indexed in Scilit:
- Apoptosis Regulators Fas and Bim Cooperate in Shutdown of Chronic Immune Responses and Prevention of AutoimmunityPublished by Elsevier ,2008
- Combined Deficiency of Proapoptotic Regulators Bim and Fas Results in the Early Onset of Systemic AutoimmunityImmunity, 2008
- Apoptosis Regulators Bim and Fas Function Concurrently to Control Autoimmunity and CD8+ T Cell ContractionImmunity, 2008
- Regulatory T cells prevent catastrophic autoimmunity throughout the lifespan of miceNature Immunology, 2006
- Suppressor of Cytokine Signaling-1 Has IFN-γ-Independent Actions in T Cell HomeostasisThe Journal of Immunology, 2003
- A rare polyadenylation signal mutation of the FOXP3 gene (AAUAAA→AAUGAA) leads to the IPEX syndromeImmunogenetics, 2001
- X-linked neonatal diabetes mellitus, enteropathy and endocrinopathy syndrome is the human equivalent of mouse scurfyNature Genetics, 2001
- Disruption of a new forkhead/winged-helix protein, scurfin, results in the fatal lymphoproliferative disorder of the scurfy mouseNature Genetics, 2001
- Signals transducers and activators of transcription (STAT)-induced STAT inhibitor-1 (SSI-1)/suppressor of cytokine signaling-1 (SOCS-1) suppresses tumor necrosis factor α-induced cell death in fibroblastsProceedings of the National Academy of Sciences, 2000
- SOCS1 Is a Critical Inhibitor of Interferon γ Signaling and Prevents the Potentially Fatal Neonatal Actions of this CytokineCell, 1999