Loss of microRNAs in thymus perturbs invariant NKT cell development and function

microRNAs(miRNAs)are small noncoding RNAs that mediate RNA interference to suppress protein expression at the translational level.Accumulated evidence indicates that miRNAs play critical roles in various biological processes and disease development,including autoimmune diseases.Invariant natural killer T(iNKT)cells are an unusual CD1d-restricted subset of thymus-derived T cells that are potent regulators of diverse immune responses.Our previous studies with the mouse model of bone marrow-specific Dicer deletion suggest the involvement of Dicer-dependent miRNAs in the development and function of iNKT cells.In the present study,to further dissect the functional levels of Dicer-dependent miRNAs in regulating iNKT cell development,we generated a mouse model with the Dicer deletion in the thymus.Our data indicate that lack of miRNAs following the deletion of Dicer in the thymus severely interrupted the development and maturation of iNKT cells in the thymus and significantly decreased the number of iNKT cells in the peripheral immune organs.miRNA-deficient peripheral iNKT cells display profound defects in activation and cytokine production upon a-galactosylceramide(a-GalCer)stimulation.Our results demonstrate a critical role of the miRNA-dependent pathway in the thymus in the regulation of iNKT cell development and function.

MicroRNAs are key regulators controlling iNKT and regulatory T-cell development and function

MicroRNAs(miRNAs)are an abundant class of evolutionarily conserved,small,non-coding RNAs that post-transcriptionally regulate expression of their target genes.Emerging evidence indicates that miRNAs are important regulators that control the development,differentiation and function of different immune cells.Both CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells and invariant natural killer T(iNKT)cells are critical for immune homeostasis and play a pivotal role in the maintenance of self-tolerance and immunity.Here,we review the important roles of miRNAs in the development and function of iNKT and Treg cells.

Types of tolerance seen in autoreactive phosphocholine-specific B cells are dependent on the idiotype of the receptors expressed

Phosphocholine （PC） is the immunodominant epitope found on the surface of a number of microorganisms, including Streptococcus pneumoniae （SPn）, and is thought to play a vital role in the pathogenesis of SPn. B cells expressing M 167Hκ24L immunoglobulin receptors specific for PC have been shown to be autoreactive in that they undergo clonal deletion in both X-linked immune-deficient and Rag-/- mice. We have now shown that B cells expressing M603HK8L PC-specific receptors also delete in Rag-/- mice, whereas those expressing T15HK22L transgenes do not delete. However, T15HK22L B cells are lost in normal heterozygous transgenic mice because they cannot compete with normal B cells. These data indicate that M167Hκ24L and M603H^8L PC-specific B cells are recognizing an autoantigen expressed on membranes which causes them to downregulate their receptors and clonally delete, while T15Hκ22L B cells are tolerized by a soluble form of PC-antigen which results in their being trapped in the spleen. Thus, the types of tolerance seen in autoreactive PC-specific B cells are dependent on the idiotype of the receptors expressed.