Differential expression of CD300a/c on human TH1 and TH17 cells

<p>Abstract</p> <p>Background</p> <p>Human memory CD4⁺T cells can be either CD300a/c⁺or CD300a/c^-and subsequent analyses showed that CD4⁺effector memory T (T_EM) cells are mostly CD300a/c⁺, whereas CD4⁺central memory T (T_CM) cells have similar frequencies of CD300a/c⁺and CD300a/c^-cells.</p> <p>Results</p> <p>Extensive phenotypical and functional characterization showed that in both T_CMand T_EMcells, the CD300a/c⁺subset contained a higher number of T_H1 (IFN-γ producing) cells. Alternatively, T_H17 (IL-17a producing) cells tend to be CD300a/c^-, especially in the T_EMsubset. Further characterization of the IL-17a⁺cells showed that cells that produce only this cytokine are mostly CD300a/c^-, while cells that produce IL-17a in combination with other cytokines, especially IFN-γ, are mostly CD300a/c⁺, indicating that the expression of this receptor is associated with cells that produce IFN-γ. Co-ligation of the TCR and CD300a/c in CD4⁺T cells inhibited Ca²⁺mobilization evoked by TCR ligation alone and modulated IFN-γ production on T_H1 polarized cells.</p> <p>Conclusion</p> <p>We conclude that the CD300a/c receptors are differentially expressed on human T_H1 and T_H17 cells and that their ligation is capable of modulating TCR mediated signals.</p

Differential effects of Cbl and 70Z/3 Cbl on T cell receptor-induced phospholipase Cγ-1 activity

AbstractWe demonstrate that the differential effects Cbl and oncogenic 70Z/3 Cbl have on Ca2+/Ras-sensitive NF-AT reporters is partially due to their opposing ability to regulate phospholipase Cγ1 (PLCγ1) activation as demonstrated by analysis of the activation of an NF-AT reporter construct and PLCγ1-mediated inositol phospholipid (PI) hydrolysis. Cbl over-expression resulted in reduced T cell receptor-induced PI hydrolysis, in the absence of any effect on PLCγ1 tyrosine phosphorylation. In contrast, expression of 70Z/3 Cbl led to an increase in basal and OKT3-induced PLCγ1 phosphorylation and PI hydrolysis. These data indicate that Cbl and 70Z/3 Cbl differentially regulate PLCγ1 phosphorylation and activation. The implications of these data on the mechanism of Cbl-mediated signaling regulation are discussed

Phospholipase C–mediated hydrolysis of PIP2 releases ERM proteins from lymphocyte membrane

Mechanisms controlling the disassembly of ezrin/radixin/moesin (ERM) proteins, which link the cytoskeleton to the plasma membrane, are incompletely understood. In lymphocytes, chemokine (e.g., SDF-1) stimulation inactivates ERM proteins, causing their release from the plasma membrane and dephosphorylation. SDF-1–mediated inactivation of ERM proteins is blocked by phospholipase C (PLC) inhibitors. Conversely, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) levels by activation of PLC, expression of active PLC mutants, or acute targeting of phosphoinositide 5-phosphatase to the plasma membrane promotes release and dephosphorylation of moesin and ezrin. Although expression of phosphomimetic moesin (T558D) or ezrin (T567D) mutants enhances membrane association, activation of PLC still relocalizes them to the cytosol. Similarly, in vitro binding of ERM proteins to the cytoplasmic tail of CD44 is also dependent on PIP2. These results demonstrate a new role of PLCs in rapid cytoskeletal remodeling and an additional key role of PIP2 in ERM protein biology, namely hydrolysis-mediated ERM inactivation

Human Th1 Cells That Express CD300a Are Polyfunctional and After Stimulation Up-Regulate the T-Box Transcription Factor Eomesodermin

Human naïve CD4 T cells express low levels of the immunomodulatory receptor CD300a, whereas effector/memory CD4 cells can be either CD300a+ or CD300a−. This suggested that CD300a expression could define a specific subset within the effector/memory CD4 T cell subpopulations. In fact, ex vivo analysis of the IFN-γ producing CD4 T cells showed that they are enriched in the CD300a+ subset. Moreover, stimulated CD4 T cells producing TNF-α and IL-2 besides IFN-γ (polyfunctional) are predominantly CD300a+. In addition to producing markedly higher levels of Th1-associated cytokines, the stimulated CD300a+ CD4 T cells are distinguished by a striking up-regulation of the T-box transcription factor eomesodermin (Eomes), whereas T-bet is up-regulated in both CD300a+ and CD300a− activated CD4 T cells to similar levels. The pleiotropic cytokine TGF-β1 has a determinant role in dictating the development of this Th1 subset, as its presence inhibits the expression of CD300a and down-regulates the expression of Eomes and IFN-γ. We conclude that CD300a+ human Th1 cells tend to be polyfunctional and after stimulation up-regulate Eomes

Tracking fine-scale structural changes in coastal dune morphology using kite aerial photography and uncertainty-assessed Structure-from-Motion photogrammetry (dataset)

The data includes aerial photos of a section of St. Gothian Dunes sand dune system (North Cornwall, UK) at 6 different periods of time. Six of the datasets are obtained with kite aerial photography and one has been captured with a lightweight drone. Photos are processed and ready to be used with Agisoft Photoscan to produce dense point clouds. Also included are the positions of Ground Control Points for each survey as well as vector data indicating the areas investigated. Lastly, change clouds (processed data) from the M3C2-PM process are included.The article associated with this dataset is located in ORE at: http://hdl.handle.net/10871/34019This is the dataset used for the Duffy et al. (2018) article "Tracking fine-scale structural changes in coastal dune morphology using kite aerial photography and uncertainty-assessed structure-from-motion photogrammetry" published in Remote Sensing.This research was funded by [Natural Environment Research Council] grant number [570009815