I787 provides signals for c-Kit receptor internalization and functionality that control mast cell survival and development.

Mast cell (MC) differentiation, survival, and activation are controlled by the membrane tyrosine kinase c-Kit upon interaction with stem cell factor (SCF). Here we describe a single point mutation induced by N-ethyl-N-nitrosurea (ENU) mutagenesis in C57BL/6J mice-an A to T transversion at position 2388 (exon 17) of the c-Kit gene, resulting in the isoleucine 787 substitution by phenylalanine (787F), and analyze the consequences of this mutation for ligand binding, signaling, and MC development. The Kit(787F/787F) mice carrying the single amino acid exchange of c-Kit lacks both mucosal and connective tissue-type MCs.

Transcriptional regulation of mouse mast cell protease-2 by interleukin-15.

Mast cells (MCs) play a critical role in innate and adaptive immunity through the release of cytokines, chemokines, lipid mediators, biogenic amines, and proteases. We recently showed that the activities of MC proteases are transcriptionally regulated by intracellularly retained interleukin-15 (IL-15), and we provided evidence that this cytokine acts as a specific regulator of mouse mast cell protease-2 (mMCP-2). Here, we show that in wild-type bone marrow-derived mast cells (BMMCs) IL-15 inhibits mMCP-2 transcription indirectly by inducing differential expression and mMCP-2 promoter binding of the bifunctional transcription factors C/EBPbeta and YY1.

Intracellular IL-15 controls mast cell survival.

The regulation of mast cell activities and survival is a central issue in inflammatory immune responses. Here, we have investigated the role of mouse interleukin-15, a pro-inflammatory and pleiotropic cytokine, in the control of mast cell survival and homeostasis. We report that aged IL-15-/- mice show a reduced number of peritoneal mast cells compared to WT mice.

IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities.

Sepsis remains a global clinical problem. By using the mouse cecal ligation and puncture model of sepsis, here we identify an important aspect of mast cell (MC)-dependent, innate immune defenses against Gram-negative bacteria by demonstrating that MC protease activity is regulated by interleukin-15 (IL-15). Mouse MCs express both constitutive and lipopolysaccharide-inducible IL-15 and store it intracellularly.

Correlation among loss of heterozygosity, promoter methylation and protein expression of MLH1 in larynx cancer.

Extensive molecular studies in development of the squamous cell carcinoma of larynx (SCCL) indicated the involvement of a variety of genes including the MLH1. To search for possible mechanism leading to MLH1 silencing in SCCL we studied LOH and promoter methylation in a homogeneous set of 62 larynx cancers. Then we evaluated immunohistochemically the MLH1 expression for 51 tumor specimens.

Dendritic cell-derived IL-15 controls the induction of CD8 T cell immune responses.

The development and the differentiation of CD8(+) T cells are dependent on IL-15. Here, we have studied the source and mechanism of how IL-15 modulates CD8(+) T cell-mediated Th1 immune responses by employing two delayed-type hypersensitivity (DTH) models. IL-15-deficient (IL-15(-/-)) mice or mice treated with soluble IL-15Ralpha as an IL-15 antagonist showed significantly reduced CD8(+) T cell-dependent DTH responses, while activation of CD4(+) T cell and B cell functions remained unaffected.

Uncommon cytidine-homopolymer dimorphism in 5'-UTR of the human otoferlin gene.

Human otoferlin, homologous to the Caenorhabditis elegans spermatogenesis factor FER-1 that was shown to be involved in membrane vesicle fusion, belongs to a group of membrane-anchored cytosolic proteins and is found expressed in brain, cochlear inner hair cells and vestibular type I sensory cells. Nonsense and missense mutations of OTOF lead to an autosomal recessive deafness phenotype (DFNB9). We describe here an unusual C-homopolymer dimorphism at position -136 of 5'-UTR of the OTOF short splice form.

Second family with hearing impairment linked to 19q13 and refined DFNA4 localisation.

Until now, over 30 loci have been identified by linkage analysis of affected families that segregate non-syndromic and dominantly inherited forms of hearing impairment (DFNA). A German family with a non-syndromic progressive hearing impairment transmitted in autosomal dominant mode was linked to 19q13.3-q13.