Selective Imprinting of Gut-Homing T Cells by Peyer's Patch Dendritic Cells, Nature 424, 88-93

The Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature (Impact Factor: 41.46). 08/2003; 424(6944):88-93. DOI: 10.1038/nature01726
Source: PubMed


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.

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    • "The chemokine system is an intricate network of related cytokines and their cognate receptors, which together play a key role in the directed migration of leukocytes to their site of action [1] [2]. Expression of both the chemokine receptor CCR9 and the integrin í µí»¼ 4 í µí»½ 7 is required for efficient lymphocyte homing to the intestine; these proteins form the socalled gut-homing phenotype of intestinal lymphocytes [3] [4]. CCR9 is expressed on the majority of CD4 + (67%) and CD8 + (54%) T cells [5] as well as B cells [4] and plasmacytoid dendritic cells [6] [7] isolated from the small intestine. "
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    ABSTRACT: While it has long been established that the chemokine receptor CCR9 and its ligand CCL25 are essential for the movement of leukocytes into the small intestine and the development of small-intestinal inflammation, the role of this chemokine-receptor pair in colonic inflammation is not clear. Toward this end, we compared colonic CCL25 protein levels in healthy individuals to those in patients with ulcerative colitis. In addition, we determined the effect of CCR9 pharmacological inhibition in the mdr1a −/− mouse model of ulcerative colitis. Colon samples from patients with ulcerative colitis had significantly higher levels of CCL25 protein compared to healthy controls, a finding mirrored in the mdr1a −/− mice. In the mdr1a −/− mice, CCR9 antagonists significantly decreased the extent of wasting and colonic remodeling and reduced the levels of inflammatory cytokines in the colon. These findings indicate that the CCR9:CCL25 pair plays a causative role in ulcerative colitis and suggest that CCR9 antagonists will provide a therapeutic benefit in patients with colonic inflammation.
    Mediators of Inflammation 10/2015; 2015(5):628340. DOI:10.1155/2015/628340 · 3.24 Impact Factor
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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 [37] [38], or cell imprinting technique [39]. 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. "
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    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). "
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    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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