Selective Imprinting of Gut-Homing T Cells by Peyer's Patch Dendritic Cells, Nature 424, 88-93
ABSTRACT Whereas naive T cells migrate only to secondary lymphoid organs, activation by antigen confers to T cells the ability to home to non-lymphoid sites. Activated effector/memory T cells migrate preferentially to tissues that are connected to the secondary lymphoid organs where antigen was first encountered. Thus, oral antigens induce effector/memory cells that express essential receptors for intestinal homing, namely the integrin alpha4beta7 and CCR9, the receptor for the gut-associated chemokine TECK/CCL25 (refs 6, 8, 9). Here we show that this imprinting of gut tropism is mediated by dendritic cells from Peyer's patches. Stimulation of CD8-expressing T cells by dendritic cells from Peyer's patches, peripheral lymph nodes and spleen induced equivalent activation markers and effector activity in T cells, but only Peyer's patch dendritic cells induced high levels of alpha4beta7, responsiveness to TECK and the ability to home to the small intestine. These findings establish that Peyer's patch dendritic cells imprint gut-homing specificity on T cells, and thus license effector/memory cells to access anatomical sites most likely to contain their cognate antigen.
- SourceAvailable from: Dong-Myeong Shin
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- "It is important to note that we acquired capacitance data from a colony of cells rather than from an individual cell. A single cell can be cultured with a smaller gap design and cell manipulation between electrodes using optical cell trapping  , or cell imprinting technique . However, the average of data from a Fig. 3. Normalized capacitance difference of L-929 cells treated with different concentration (0; orange, 0.17 M; red, 0.83 M; navy, 3.33 M; dark yellow) of EGF over time. "
ABSTRACT: We developed a capacitance sensor with parallel plate geometry to measure epithermal growth factor receptor (EGFR) expression levels on cell membrane in real-time. We first proved correlations between capacitance changes and cell numbers settled down between electrodes, and then observed capacitance changes elicited by interactions between EGFR on membrane and EGF proteins in real time. Consequently, we confirmed that the EGFR expression levels of varied typed cells were successfully quantified. This approach can effectively distinguish differences of EGFR levels of cancer cells and normal cells in real-time. Also, up to 600% sensitivity enhancements and around 2.2 h on average sensing time saving were achieved by using the capacitance sensor over a conventional immunoassay technique. Such a capacitance biosensor can be extended to broad fields where the receptor–antibody reactions, the receptor–virus reactions or DNA hybridizations are involved.Sensors and Actuators B Chemical 03/2015; 209. DOI:10.1016/j.snb.2014.12.001 · 4.10 Impact Factor
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- "Retinoic acid has been shown to inhibit Th17 and the conversion of Tregs into T follicular helper cells, and induce intestinal mucosal homing molecules CCR9 and a 4 b 7 (Benson et al. 2007; Iwata et al. 2004; Mora et al. 2003; Mucida et al. 2007; Sun et al. 2007; Takahashi et al. 2012). Also, retinoic acid is important for IgA-secreting cells, since mice deficient for vitamin A lack these cells in the small intestine (Mora et al. 2006). "
ABSTRACT: Our environment poses a constant threat to our health. To survive, all organisms must be able to discriminate between good (food ingredients and microbes that help digest our food) and bad (pathogenic microbes, viruses and toxins). In vertebrates, discrimination between beneficial and harmful antigens mainly occurs at the mucosal surfaces of the respiratory, digestive, urinary and genital tract. Here, an extensive network of cells and organs form the basis of what we have come to know as the mucosal immune system. The mucosal immune system is composed of a single epithelial cell layer protected by a mucus layer. Different immune cells monitor the baso-lateral side of the epithelial cells and dispersed secondary lymphoid organs, such as Peyer's patches and isolated lymphoid follicles are equipped with immune cells able to mount appropriate and specific responses. This review will focus on the current knowledge on host, dietary and bacterial-derived factors that shape the mucosal immune system before and after birth. We will discuss current knowledge on fetal immunity (both responsiveness and lymphoid organ development) as well as the impact of diet and microbial colonization on neonatal immunity and disease susceptibility. Lastly, inflammatory bowel disease will be discussed as an example of how the composition of the microbiota might predispose to disease later in life. A fundamental understanding of the mechanisms involved in mucosal immune development and tolerance will aid nutritional intervention strategies to improve health in neonatal and adult life.Archivum Immunologiae et Therapiae Experimentalis 02/2015; 63(4). DOI:10.1007/s00005-015-0329-y · 3.18 Impact Factor
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- "This cell subset has little if any CD4 expression, eliminating the interference of CD4 mediated binding. PBMCs were stimulated for α 4 β 7 expression by retinoic acid (RA) (Mora J R, et al., 2003). Activated PBMCs from three different donors were subjected to sorting based on CD8 and β 7 expression by FCM (dot plot of Figure 2D). "
ABSTRACT: HIV-1 envelope glycoprotein is reported to interact with α4β7, an integrin mediating the homing of lymphocytes to gut-associated lymphoid tissue, but the significance of α4β7 in HIV-1 infection remains controversial. Here, using HIV-1 strain BaL, the gp120 of which was previously shown to be capable of interacting with α4β7, we demonstrated that α4β7 can mediate the binding of whole HIV-1 virions to α4β7-expressing transfectants. We further constructed a cell line stably expressing α4β7 and confirmed the α4β7-mediated HIV-1 binding. In primary lymphocytes with activated α4β7 expression, we also observed significant virus binding which can be inhibited by an anti-α4β7 antibody. Moreover, we investigated the impact of antagonizing α4β7 on HIV-1 infection of primary CD4(+) T cells. In α4β7-activated CD4(+) T cells, both anti-α4β7 antibodies and introduction of short-hairpin RNAs specifically targeting α4β7 resulted in a decreased HIV-1 infection. Our findings indicate that α4β7 may serve as an attachment factor at least for some HIV-1 strains. The established approach provides a promising means for the investigation of other viral strains to understand the potential roles of α4β7 in HIV-1 infection.Virologica Sinica 12/2014; 29(6):381-92. DOI:10.1007/s12250-014-3525-8