IκB kinase β–induced phosphorylation of CARMA1 contributes to CARMA1–Bcl10–MALT1 complex formation in B cells

Protein kinase C (PKC) β has been reported (Shinohara, H., T. Yasuda, Y. Aiba, H. Sanjo, M. Hamadate, H. Watarai, H. Sakurai, and T. Kurosaki. 2005. J. Exp. Med. 202:1423–1431; Sommer, K., B. Guo, J.L. Pomerantz, A.D. Bandaranayake, M.E. Moreno-Garcia, Y.L. Ovechkina, and D.J. Rawlings. 2005. Immunity. 23:561–574) to play a crucial role in B cell receptor (BCR)–mediated IκB kinase (IKK) activation through phosphorylation of caspase recruitment domain 11, Bimp3 (CARMA1). However, it remains unclear whether this PKCβ-mediated phosphorylation accounts fully for the activation status of CARMA1, because involvement of other kinases, such as phosphoinositide 3-kinase–dependent kinase 1, has also been suggested. We show that PKCβ mediates phosphorylation of CARMA1 on Ser668, which in turn is essential for BCR-mediated CARMA1–Bcl10–mucosal-associated lymphoid tissue 1 (MALT1) association and subsequent IKK activation. Our analyses also demonstrate that the downstream kinase IKKβ contributes to facilitating formation of the complex CARMA1–Bcl10–MALT1 by mediating phosphorylation of CARMA1. Hence, our data suggest that PKCβ is crucial for initial activation of IKK. The activated IKKβ does not merely function as an effector enzyme but also modifies the upstream signaling complex through a feedback mechanism, thereby optimizing the strength and duration of the nuclear factor κB signal

Heat shock cognate protein 70 contributes to Brucella invasion into trophoblast giant cells that cause infectious abortion

<p>Abstract</p> <p>Background</p> <p>The cell tropism of <it>Brucella abortus</it>, a causative agent of brucellosis and facultative intracellular pathogen, in the placenta is thought to be a key event of infectious abortion, although the molecular mechanism for this is largely unknown. There is a higher degree of bacterial colonization in the placenta than in other organs and many bacteria are detected in trophoblast giant (TG) cells in the placenta. In the present study, we investigated mechanism of <it>B. abortus </it>invasion into TG cells.</p> <p>Results</p> <p>We observed internalization and intracellular growth of <it>B. abortus </it>in cultured TG cells. A monoclonal antibody that inhibits bacterial internalization was isolated and this reacted with heat shock cognate protein 70 (Hsc70). Depletion and over expression of Hsc70 in TG cells inhibited and promoted bacterial internalization, respectively. IFN-γ receptor was expressed in TG cells and IFN-γ treatment enhanced the uptake of bacteria by TG cells. Administering the anti-Hsc70 antibody to pregnant mice served to prevent infectious abortion.</p> <p>Conclusion</p> <p><it>B. abortus </it>infection of TG cells in placenta is mediated by Hsc70, and that such infection leads to infectious abortion.</p

AKARI infrared imaging of reflection nebulae IC4954 and IC4955

We present the observations of the reflection nebulae IC4954 and IC4955 region with the Infrared Camera (IRC) and the Far-Infrared Surveyor (FIS) on board the infrared astronomical satellite AKARI during its performance verification phase. We obtained 7 band images from 7 to 160um with higher spatial resolution and higher sensitivities than previous observations. The mid-infrared color of the S9W (9um) and L18W (18um) bands shows a systematic variation around the exciting sources. The spatial variation in the mid-infrared color suggests that the star-formation in IC4954/4955 is progressing from south-west to north-east. The FIS data also clearly resolve two nebulae for the first time in the far-infrared. The FIS 4-band data from 65um to 160um allow us to correctly estimate the total infrared luminosity from the region, which is about one sixth of the energy emitted from the existing stellar sources. Five candidates for young stellar objects have been detected as point sources for the first time in the 11um image. They are located in the red S9W to L18W color regions, suggesting that current star-formation has been triggered by previous star-formation activities. A wide area map of the size of about 1 x 1 (deg^2) around the IC4954/4955 region was created from the AKARI mid-infrared all-sky survey data. Together with the HI 21cm data, it suggests a large hollow structure of a degree scale, on whose edge the IC4954/4955 region has been created, indicating star formation over three generations in largely different spatial scales.Comment: 23 pages, 7 figures, accepted for publication in PASJ AKARI special issu

Regulation of T helper type 2 cell differentiation by murine Schnurri-2

Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor β, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2–deficient mice, mature peripheral T cells exhibited normal anti–T cell receptor–induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2–deficient developing Th2 cells showed constitutive activation of nuclear factor κB (NF-κB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-κB for binding to a consensus NF-κB motif and inhibit NF-κB–driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-κB function

Identification of CD4−CD8− Double-Negative Natural Killer T Cell Precursors in the Thymus

BACKGROUND: It is well known that CD1d-restricted Valpha14 invariant natural killer T (NKT) cells are derived from cells in the CD4(+)CD8(+) double-positive (DP) population in the thymus. However, the developmental progression of NKT cells in the earlier stages remains unclear, and the possible existence of NKT cell presursors in the earlier stages than DP stage remains to be tested. PRINCIPAL FINDINGS: Here, we demonstrate that NKT cell precursors that express invariant Valpha14-Jalpha18 transcripts but devoid of surface expression of the invariant Valpha14 receptor are present in the late CD4(-)CD8(-) double-negative (DN)4 stage and have the potential to generate mature NKT cells in both in vivo and in vitro experimental conditions. Moreover, the DN4 population in CD1d knock-out (CD1dKO) mice was similar to those with an NKT cell potential in wild-type (WT) C57BL/6 (B6) mice, but failed to develop into NKT cells in vitro. However, these precursors could develop into NKT cells when co-cultured with normal thymocytes or in an in vivo experimental setting, indicating that functional NKT cell precursors are present in CD1dKO mice. CONCLUSIONS: Together, these results demonstrate that thymic DN4 fraction contains NKT cell precursors. Our findings provide new insights into the early development of NKT cells prior to surface expression of the invariant Valpha14 antigen receptor and suggest the possible alternative developmental pathway of NKT cells