China 
Africa 
Explore chapters and articles related to this topic
Pathways of Cell Recruitment to Mucosal Surfaces
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
Additional mAb were generated; the β chain was cloned and subsequently identified as the β7 integrin, a novel chain restricted in expression to hematopoiteic lineages (61–63). Interestingly, the notion of α4β7 as the Peyer’s patch homing receptor was subsequently dismissed after these initial experiments as the anti-a4 mAb Rl-2 mAb failed to block adhesion of TK1 cells to affinity-purified mucosal addressin (see below). Only after additional mAbs were generated was the relationship of α4β7 to mucosal addressin cell adhesion molecule-1 (MAdCAM-I) reexamined and firmly established (64,65). The anti-a4 mAb PS/2 and anti-α7 mAbs FIB 22, DATK 32 (which sees a combinatorial epitope of α4β7), and anti-α7 mAb M301 all were shown to block binding of TK1 cells to affinity-purified MAdCAM-1 and CHO cells transfected with recently cloned MAdCAM-1 cDNA (64) (see below). These data confirmed that α4β7 is identical to the previously described Peyer’s patch homing receptor LPAM 1 and is a ligand for MAdCAM-1. Studies with the anti-human α4β7 mAb Act-1 (57) have shown that for both CD4+ and CD8+ T cells and B-cell subsets, α4β7 represents a unique mucosal subpopulation (56,58,59)
Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Asmita Hazra, Saptarshi Mandal
The α4β1 (VLA4) and α4β7 integrins are important leukocyte homing (organ “addressin”-specific targeting) receptors. The main ligands of these two integrins are VCAM1 and fibronectin. Α4β7 can also bind to MAdCAM1 in high endothelial venules of mucosal lymphoid organs, which cause mucosa-specific homing. Another integrin α6β1 is also important in leukocyte firm adhesion and transmigration in general.
Mucosal vaccine strategies
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Nils Lycke, Jan Holmgren, Harry B. Greenberg
Antigen-triggered B and T cells in the inductive site, such as the nasopharynx-associated lymphoid tissue (NALT) or the PPs, leave the site of initial antigen encounter, transit through the lymph, enter the blood circulation, and then seed the nonorganized lamina propria of the mucosal membrane at selected sites (Figure 30.1). Hence, there is a distinct compartmentalization for antigen-activated T and B cells, which home preferentially to the mucosa of origin where they differentiate into effector T cells and plasma cells, respectively. The anatomical affinity of such cells is determined through site-specific integrins—“homing receptors” (α4β7) and chemokine receptors (CCR9, CCR10) on mucosal lymphoid cells—and the complementary tissue-specific endothelial cell adhesion molecules (“addressins”) and chemokines that are expressed differentially in the various mucosal tissues. For instance, gut-homing PP IgA B cells and plasmablasts, as well as mucosal CD4+ and CD8+ T cells, express α4β7 integrin that can specifically attach to vascular mucosal addressin cell adhesion molecule-1, a tissue-specific addressin expressed selectively on the high endothelial venules in the gut intestinal mucosa. As mentioned previously, the homing properties are imprinted on the antigen-activated lymphocytes by mucosal DCs acting at the inductive sites, more specifically in the PPs and MLN. Interestingly, this property is the function of CD103+ DCs and is directly dependent on their ability to metabolize vitamin A because the concentration of retinoic acid appears to be responsible for the induction of Aldh1a2 expression and aldehyde dehydrogenase activity, which have been linked to the imprinting properties of these DCs. During this process, DCs can also be influenced by epithelial cells that produce cofactors (such as IFNλ) in response to pathogens, which may then indirectly affect homing and differentiation of specific B and T cells. An example of such a cofactor-induced molecule is thymic stromal lymphopoietin (TSLP), which appears to promote DC-priming of IL 4-producing follicular helper T (Tfh) cells. Moreover, chemokines produced by epithelial cells promote chemotaxis of immune cells with cognate chemokine receptors. For instance, colon CCL28, also known as mucosa-associated epithelial chemokine, selectively attracts IgA B cells and plasmablasts expressing the chemokine receptor CCR10; whereas CCL25 (TECK), which is abundantly produced in the small intestine, can selectively attract B and T cells expressing the CCR9 receptor to preferentially disseminate from the blood into the small intestinal mucosa. Thus, homing and chemokine receptors selectively expressed on antigen-activated lymphocytes (e.g., α4β7, CCR9, and CCR10) and addressins and chemokines produced in the mucosal membrane help explain both the segregation of secretory immune responses from systemic immune responses and the preferential dissemination of T- and B-cell responses to uniquely compartmentalized mucosal sites.
Promising phase II biologics for future Crohn’s disease therapy
Published in Expert Opinion on Investigational Drugs, 2023
Pauline Wils, Silvio Danese, Laurent Peyrin-Biroulet
The α4ß7 integrin present on lymphocytes interacts with the mucosal vascular addressin cell adhesion molecule (MAdCAM-1). MAdCAM-1 is expressed on the vascular endothelium under the intestinal lamina propria and intestinal lymphoid tissues, allowing their migration into the gut and causing inflammation [34–36]. Interestingly MAdCAM-1 is not expressed in the central nervous system [36]. MAdCAM-1 expression is upregulated in CD patients and has been shown to play a role in chronic inflammation of the intestinal mucosa in IBD patients [35]. Anti-adhesion therapies that target α4 integrins (vedolizumab and natalizumab) are approved for CD treatment, blocking T-cell recruitment to the intestinal tissues. Natalizumab targets both α4ß7 and α1ß7 integrins and consequently blocks also the recruitment of leukocytes across the blood-brain barrier [18].
Examining the role of nickel and NiTi nanoparticles promoting inflammation and angiogenesis
Published in Journal of Immunotoxicology, 2022
Anup K. Srivastava, Dustin M. Snapper, Jiwen Zheng, Banu S. Yildrim, Sandeep Srivastava, Steven C. Wood
The present study focused on determining the presence in angioreactors of cells bearing CD31, a platelet endothelial cell adhesion molecule that is a well-characterized mechano-sensor of shear stress. In addition, cells were counterstained for MADCAM (mucosal vascular addressin cell adhesion molecule-1) protein that is also expressed on high endothelial venules and binds to counter receptors and VLA-4 (α4β1), L-selectin, and leukocyte β7 integrin LPAM-1 (α4β7) (Rivera-Nieves et al. 2008). The data here showed NiTi NP induced angiogenesis to a level 4–5-fold above background and that this was most likely associated with inflammatory processes triggered by cytokine release. Neovessel development by endothelial cells is driven in great part by VEGF and FGF cytokines (Cao et al. 2004). Of note, each of these cytokines are induced to be released from M2 macrophages by hypoxia (and thus, HIF-1α). Both are also released from activated macrophages and endothelial cells. Based on the findings here, it is clear that biomaterials/particulates have a potential to induce profound effects on neo-angiogenesis and re-vascularization processes. The results here are the first to show that nickel (in the context of an NP form) can impact on both processes, and actually act to stimulate angiogenesis in situ.
In situ thermal ablation augments antitumor efficacy of adoptive T cell therapy
Published in International Journal of Hyperthermia, 2019
Fumito Ito, Trupti D. Vardam, Michelle M. Appenheimer, Kevin H. Eng, Sandra O. Gollnick, Jason B. Muhitch, Sharon S. Evans
CD8+ T cells at a density of 5 × 107 cells per ml were labeled for 20 min at 37 °C with 180 μg/ml of TRITC (tetramethylrhodamine-6-isothiocyanate; Molecular Probes, Eugene, OR, USA) in RPMI 1640 medium (Invitrogen) and labeling was stopped by centrifugation through a 'cushion' of FCS (Invitrogen) [15,45,47,48]. Within a given experiment, equivalent numbers of labeled cells (1–2 × 107 cells per mouse in 300 μl PBS) were injected intravenously (iv) via the tail vein into RFA- or sham-treated mice bearing 10–11 day established tumors. Organs were collected 1 or 12 h after cell transfer, embedded in OCT freezing medium, and snap-frozen in liquid nitrogen. Tissues were counterstained with primary Ab specific for vascular markers to demark the position of peripheral lymph node addressin-positive (PNAd+) HEV in LN (i.e., MECA79 Ab, 20 µg/ml, BD Biosciences) or CD31+ vessels in tumors, pancreas, or spleen (MEC13.1 Ab, 20 µg/ml, BD Biosciences). After washing, primary Ab was detected by fluorochrome-conjugated (fluorescein) goat-anti-rat IgM, or goat-anti-rat IgG, respectively (Jackson ImmunoResearch, Laboratories, Inc., West Grove, PA, USA). The number of fluorescence-labeled transferred cells was quantified, double-blinded, using a BH2/RFL fluorescence microscope (Olympus Optical, Center Valley, PA, USA) in ≥10 fields (unit area of each field, 0.34 mm2) of non-sequential cryosections 9 μm in thickness.