The protein tyrosine kinase Tec regulates a CD44highCD62L- Th17 subset

The generation of Th17 cells has to be tightly controlled during an immune response. In this study, we report an increase in a CD44 2 effector/memory Th17 populations

Identification of the molecular signatures integral to regenerating photoreceptors in the retina of the zebra fish

Investigating neuronal and photoreceptor regeneration in the retina of zebra fish has begun to yield insights into both the cellular and molecular means by which this lower vertebrate is able to repair its central nervous system. However, knowledge about the signaling molecules in the local microenvironment of a retinal injury and the transcriptional events they activate during neuronal death and regeneration is still lacking. To identify genes involved in photoreceptor regeneration, we combined light-induced photoreceptor lesions, laser-capture microdissection of the outer nuclear layer (ONL) and analysis of gene expression to characterize transcriptional changes for cells in the ONL as photoreceptors die and are regenerated. Using this approach, we were able to characterize aspects of the molecular signature of injured and dying photoreceptors, cone photoreceptor progenitors, and microglia within the ONL. We validated changes in gene expression and characterized the cellular expression for three novel, extracellular signaling molecules that we hypothesize are involved in regulating regenerative events in the retina

Pax5: the guardian of B cell identity and function

The transcription factor Pax5 is essential for commitment of lymphoid progenitors to the B lymphocyte lineage. Pax5 fulfils a dual role by repressing B lineage 'inappropriate' genes and simultaneously activating B lineage–specific genes. This transcriptional reprogramming restricts the broad signaling capacity of uncommitted progenitors to the B cell pathway, regulates cell adhesion and migration, induces VH-DJH recombination, facilitates (pre-)B cell receptor signaling and promotes development to the mature B cell stage. Conditional Pax5 inactivation in early and late B lymphocytes revealed an essential role for Pax5 in controlling the identity and function of B cells throughout B lymphopoiesis. PAX5 has also been implicated in human B cell malignancies, as it is deregulated by chromosomal translocations in a subset of acute lymphoblastic leukemias and non-Hodgkin lymphomas.<br/

Altered CD4/CD8 cell fate decision in the absence of MAZR due to redirected differentiation of MHC class I-restricted thymocytes (85.9)

Abstract Cell fate specifications during thymocyte differentiation are linked with the tightly controlled expression of CD4 and CD8. We have previously identified that the transcriptional regulator MAZR is an important regulator of the activation of the Cd8ab gene complex during the DN to DP transition. To investigate the role of MAZR in more detail, MAZR-/- mice were generated. MAZR-/- mice were smaller in size and were born at reduced mendelian frequency. MAZR-/- DN thymocytes did not show premature expression of CD8, indicating that the deletion of MAZR is not sufficient to activate CD8 expression in DN cells. However, variegated CD8 expression in DP thymocytes of Cd8 enhancer E8I,E8II doubly deficient mice was dramatically reduced in the absence of MAZR. In addition, we observed elevated CD4/CD8 ratios in thymocytes and in peripheral T cells of MAZR-/- mice. Using MHC class I-restricted TCR transgenic mice, we demonstrated that the altered CD4/8 ratio in MAZR-/- mice was, in part, due to redirected differentiation of a fraction of MHC-class I restricted thymocytes into the CD4 lineage. Thus, our data provide genetic evidence that MAZR controls CD8 expression during thymocyte development. In addition, our results may indicate that MAZR is part of the transcription factor network that controls CD4/CD8 cell fate decisions of DP thymocytes. Supported by the Austrian Science Fund (P19930, SFB-F2305 and START Program Y-163).</jats:p

Transcription Factor Pax5 Activates the Chromatin of Key Genes Involved in B Cell Signaling, Adhesion, Migration, and Immune Function

SummaryThe transcription factor Pax5 represses B lineage-inappropriate genes and activates B cell-specific genes in B lymphocytes. Here we have identified 170 Pax5-activated genes. Conditional mutagenesis demonstrated that the Pax5-regulated genes require continuous Pax5 activity for normal expression in pro-B and mature B cells. Expression of half of the Pax5-activated genes is either absent or substantially reduced upon Pax5 loss in plasma cells. Direct Pax5 target genes were identified based on their protein synthesis-independent activation by a Pax5-estrogen receptor fusion protein. Chromatin immunoprecipitation (ChIP) of Pax5 together with chromatin profiling by ChIP-on-chip analysis demonstrated that Pax5 directly activates the chromatin at promoters or putative enhancers of Pax5 target genes. The Pax5-activated genes code for key regulatory and structural proteins involved in B cell signaling, adhesion, migration, antigen presentation, and germinal-center B cell formation, thus revealing a complex regulatory network that is activated by Pax5 to control B cell development and function