EBF1-deficient bone marrow stroma elicits persistent changes in HSC potential

Crosstalk between mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) is essential for hematopoietic homeostasis and lineage output. Here, we investigate how transcriptional changes in bone marrow (BM) MSCs result in long-lasting effects on HSCs. Single-cell analysis of Cxcl12-abundant reticular (CAR) cells and PDGFRα+Sca1+ (PαS) cells revealed an extensive cellular heterogeneity but uniform expression of the transcription factor gene Ebf1. Conditional deletion of Ebf1 in these MSCs altered their cellular composition, chromatin structure and gene expression profiles, including the reduced expression of adhesion-related genes. Functionally, the stromal-specific Ebf1 inactivation results in impaired adhesion of HSCs, leading to reduced quiescence and diminished myeloid output. Most notably, HSCs residing in the Ebf1-deficient niche underwent changes in their cellular composition and chromatin structure that persist in serial transplantations. Thus, genetic alterations in the BM niche lead to long-term functional changes of HSCs

Extension of the Space Experiment GRIS Onboard the ISS Capabilities: Registration of Short Gamma-ray Bursts and TGF

The unique capabilities of the detector, based on the CeBr3 crystal (very short flashing time) allow us to expand the range of problems solved in the GRIS experiment. In addition to registering solar flares that have characteristic times per second÷minute, this detector allows solving problems in identifying and recording characteristics of geophysical and astrophysical events (short gamma-ray bursts - SGRB and terrestial gamma-ray flares - TGF) in the time range of 10μs÷1 ms. The modification of the hardware of the GRIS device for solving these problems is described and discussed in this paper

Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and beta 1-integrin function

Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 cochaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells. By analyzing Mzb1 -/- Prdm1 +/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of antibody-secreting cells in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1 -/- plasmablasts show a reduced activation of β1-integrin, which contributes to the impaired plasmablast differentiation and migration of antibody-secreting cells to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation

Eomesodermin Expression in CD4⁺

CD4+ T cells polarize into effector Th subsets characterized by signature transcription factors and cytokines. Although T-bet drives Th1 responses and represses the alternative Th2, Th17, and Foxp3+ regulatory T cell fates, the role of the T-bet-related transcription factor eomesodermin (Eomes) in CD4+ T cells is less well understood. In this study, we analyze the expression and effects of Eomes in mouse CD4++ Th1 T cells in vivo. Eomes+ CD4+ T cells accumulated in old mice, under lymphopenic conditions in a T cell transfer model of colitis, and upon oral Ag administration. However, despite its expression, genetic deletion of Eomes in CD4+ T cells did not impact on IFN-γ production nor increase Th2 or Th17 responses. In contrast, Eomes deficiency favored the accumulation of Foxp3+ cells in old mice, after in vivo differentiation of Eomes-deficient naive CD4+ T cells, and in response to oral Ag in a cell-intrinsic way. Enforced Eomes expression during in vitro regulatory T cell induction also reduced Foxp3 transcription. Likewise, bystander Eomes-deficient CD4+ T cells were more efficient at protecting from experimental autoimmune encephalitis compared with wild-type CD4+ T cells. This enhanced capacity of Eomes-deficient CD4+ T cells to inhibit EAE in trans was associated with an enhanced frequency of Foxp3+ cells. Our data identify a novel role for Eomes in CD4+ T cells and indicate that Eomes expression may act by limiting Foxp3 induction, which may contribute to the association of EOMES to susceptibility to multiple sclerosis

Id3 Maintains Foxp3 Expression in Regulatory T Cells by Controlling a TranscriptionalNetwork of E47, Spi-B, and SOCS3

The transcription factor Foxp3 dominantly controls regulatory T (Treg) cell function, and only its continuous expression guarantees the maintenance of full Treg cell-suppressive capacity. However, transcriptional regulators maintaining Foxp3 transcription are incompletely described. Here, we report that high E47 transcription factor activity in Treg cells resulted in unstable Foxp3 expression. Under homeostatic conditions, Treg cells expressed high levels of the E47 antagonist Id3, thus restricting E47 activity and maintaining Foxp3 expression. In contrast, stimulation of Id3-deficient or E47-overexpressing Treg cells resulted in the loss of Foxp3 expression in a subset of Treg cells in vivo and in vitro. Mechanistic analysis indicated that E47 activated expression of the transcription factor Spi-B and the suppressor of cytokine signaling 3 (SOCS3), which both downregulated Foxp3 expression. These findings demonstrate that the balance of Id3 and E47 controls the maintenance of Foxp3 expression in Treg cells and, thus, contributes to Treg cell plasticity.Funding Agencies|International Graduate Academy fellowship; Max Planck Institute; German Research Foundation [DFG SCHA 1442/3-2, SCHA 1442/5-1]; Federal Ministry of Education and Research [BMBF 01EO1303]; European Commission [FP7 PIRG08-GA-2010-276906]; Muller-Fahnenberg Stiftung</p

The Sun and heliosphere explorer - the Interhelioprobe mission

International audienceThe Interhelioprobe mission aims to investigate the inner heliosphere and the Sun from close distances (up to 0.3 AU) and from out of the ecliptic plane (up to 30°). In this paper we present the relevance of the mission and its main scientific objectives, describe the scientific payload, ballistic scenario and orbits of the spacecraft. Possibilities of scientific cooperation with other solar and heliospheric space missions are also mentioned