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https://www.readbyqxmd.com/read/28100779/intramembrane-proteolysis-of-astrotactins
#1
Hao Chang, Philip M Smallwood, John Williams, Jeremy Nathans
Astrotactins are vertebrate-specific membrane proteins implicated in neuron-glia interactions during central nervous system development and in hair follicle polarity during skin development. By studying epitope-tagged derivatives of mouse Astrotactin2 (Astn2) produced in transfected cells, we determined that the amino- and carboxy-termini reside in the extracellular space and are initially linked by two transmembrane segments and a single cytoplasmic domain. We further show that Astn2 undergoes proteolytic cleavage in the second transmembrane domain (TM2) and that a disulfide bond holds the resulting two fragments together...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28096290/the-epidermal-polarity-protein-par3-is-a-non-cell-autonomous-suppressor-of-malignant-melanoma
#2
Melina Mescher, Peter Jeong, Sina K Knapp, Matthias Rübsam, Michael Saynisch, Marina Kranen, Jennifer Landsberg, Max Schlaak, Cornelia Mauch, Thomas Tüting, Carien M Niessen, Sandra Iden
Melanoma, an aggressive skin malignancy with increasing lifetime risk, originates from melanocytes (MCs) that are in close contact with surrounding epidermal keratinocytes (KCs). How the epidermal microenvironment controls melanomagenesis remains poorly understood. In this study, we identify an unexpected non-cell autonomous role of epidermal polarity proteins, molecular determinants of cytoarchitecture, in malignant melanoma. Epidermal Par3 inactivation in mice promotes MC dedifferentiation, motility, and hyperplasia and, in an autochthonous melanoma model, results in increased tumor formation and lung metastasis...
January 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28087239/on-going-mechanical-damage-from-mastication-drives-homeostatic-th17-cell-responses-at-the-oral-barrier
#3
Nicolas Dutzan, Loreto Abusleme, Hayley Bridgeman, Teresa Greenwell-Wild, Tamsin Zangerle-Murray, Mark E Fife, Nicolas Bouladoux, Holly Linley, Laurie Brenchley, Kelly Wemyss, Gloria Calderon, Bo-Young Hong, Timothy J Break, Dawn M E Bowdish, Michail S Lionakis, Simon A Jones, Giorgio Trinchieri, Patricia I Diaz, Yasmine Belkaid, Joanne E Konkel, Niki M Moutsopoulos
Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism...
January 17, 2017: Immunity
https://www.readbyqxmd.com/read/28081153/dermal-%C3%AE-%C3%AE-t-cells-do-not-freely-re-circulate-out-of-skin-and-produce-il-17-to-promote-neutrophil-infiltration-during-primary-contact-hypersensitivity
#4
Xiaodong Jiang, Chang Ook Park, Jenna Geddes Sweeney, Min Jae Yoo, Olivier Gaide, Thomas Seth Kupper
The role of mouse dermal γδ T cells in inflammatory skin disorders and host defense has been studied extensively. It is known that dendritic epidermal T cells (DETC) have a monomorphic γδ T cell receptor (TCR) and reside in murine epidermis from birth. We asked if dermal γδ cells freely re-circulated out of skin, or behaved more like dermal resident memory T cells (TRM) in mice. We found that, unlike epidermal γδ T cells (DETC), dermal γδ cells are not homogeneous with regard to TCR, express the tissue resident T cell markers CD69 and CD103, bear skin homing receptors, and produce IL-17 and IL-22...
2017: PloS One
https://www.readbyqxmd.com/read/28035752/the-effect-of-mhc-antigen-matching-between-donors-and-recipients-on-skin-tolerance-of-vascularized-composite-allografts
#5
K Shanmugarajah, H Powell, D A Leonard, C Mallard, A Albritton, E Harrington, M A Randolph, E Farkash, D H Sachs, J M Kurtz, C L Cetrulo
The emergence of skin-containing vascularized composite allografts (VCAs) has provided impetus to understand factors affecting rejection/tolerance of skin. VCA tolerance can be established in miniature swine across haploidentical MHC barriers using mixed chimerism. As the deceased donor pool for VCAs does not permit MHC antigen matching, clinical VCAs are transplanted across varying MHC disparities. Here, we investigated whether sharing of MHC class I or class II antigens between donors and recipients influences VCA skin tolerance...
December 30, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/28029677/an-interesting-case-of-basal-cell-carcinoma-with-raynaud-s-phenomenon-following-chronic-arsenic-exposure
#6
S Gulshan, M J Rahman, R Sarkar, S Ghosh, R Hazra
Arsenic is commonly known to be associated with squamous cell carcinoma. Among the lesser known associations is basal cell carcinoma and even rarer is its effect on blood vessels causing peripheral vascular disease. Here we present a case of a 55 yr old man with ulceroproliferative lesions on scalp and forehead along with several hyperpigmented patches on trunk and extremities. He had symptoms suggestive of Raynaud's phenomenon that eventually led to digital gangrene. FNAC was done which was suggestive of basal cell carcinoma...
October 2016: JNMA; Journal of the Nepal Medical Association
https://www.readbyqxmd.com/read/28027201/incidence-and-clinical-features-of-rare-cutaneous-malignancies-in-olmsted-county-minnesota-2000-to-2010
#7
Stanislav N Tolkachjov, Adam R Schmitt, John G Muzic, Amy L Weaver, Christian L Baum
BACKGROUND: The incidence of rare cutaneous malignancies is unknown. Current estimates of rare cutaneous malignancy incidences are based on broad epidemiologic data or single institution experiences, not population-based data. OBJECTIVE: To determine the incidence of several rare nonmelanoma skin cancers. MATERIALS AND METHODS: The authors conducted a retrospective chart review of a population-based cohort between the years 2000 and 2010. Residents of Olmsted County, Minnesota, who were diagnosed with a biopsy-proven nonmelanoma skin cancer-excluding basal cell carcinoma and squamous cell carcinoma-were included in this study...
January 2017: Dermatologic Surgery: Official Publication for American Society for Dermatologic Surgery [et Al.]
https://www.readbyqxmd.com/read/28012718/skin-resident-effector-memory-cd8-cd28-t-cells-exhibit-a-pro-fibrotic-phenotype-in-patients-with-systemic-sclerosis
#8
Gang Li, Adriana T Larregina, Robyn T Domsic, Donna B Stolz, Thomas A Medsger, Robert Lafyatis, Patrizia Fuschiotti
Loss of CD28 expression by CD8+ T cells occurs with age and during chronic inflammatory conditions. CD8+CD28- T cells are a heterogeneous cell subpopulation whose function ranges from immunosuppressive to effector. Here we analyzed the role of CD8+CD28- T cells in the pathogenesis of systemic sclerosis (SSc), a connective tissue disorder characterized by autoimmunity, vasculopathy and extensive cutaneous and visceral fibrosis. We show that the frequency of CD8+CD28- T cells is increased in the blood and affected skin of SSc patients, independent of patient age, and correlates with the extent of skin fibrosis...
December 21, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28011143/dynamic-changes-in-resident-and-infiltrating-epidermal-dendritic-cells-in-active-and-resolved-psoriasis
#9
Elisa Martini, Maria Wiken, Stanley Cheuk, Irène Gallais Sérézal, Faezzah Baharom, Mona Ståhle, Anna Smed-Sörensen, Liv Eidsmo
Epidermal Langerhans cells (LCs) are spatially separated from dermal dendritic cells (DCs) in healthy human skin. In active psoriasis, maintained by local production of IL-23 and IL-17, DCs infiltrate both skin compartments. Here we show that CCR2(+) epidermal DCs (eDCs), phenotypically distinct from dermal DCs, were strictly confined to lesional psoriasis. The eDCs exceeded the number of LCs and displayed high expression of genes involved in neutrophil recruitment and the activation of keratinocytes and T cells...
December 20, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27995750/keloid-progression-a-stiffness-gap-hypothesis
#10
Chenyu Huang, Longwei Liu, Zhifeng You, Bingjie Wang, Yanan Du, Rei Ogawa
Keloids are fibroproliferative skin disorders characterised clinically by continuous horizontal progression and post-surgical recurrence and histologically by the accumulation of collagen and fibroblast ingredients. Till now, their aetiology remains clear, which may cover genetic, environmental and metabolic factors. Evidence in the involvement of local mechanics (e.g. predilection site and typical shape) and the progress in mechanobiology have incubated our stiffness gap hypotheses in illustrating the chronic but constant development in keloid...
December 19, 2016: International Wound Journal
https://www.readbyqxmd.com/read/27992082/the-expanding-microrna-world-in-psoriasis
#11
Enikö Sonkoly
Psoriasis skin lesions are characterized by dramatic changes in the transcriptome, reflecting altered activity of multiple signaling pathways in resident and infiltrating cells. MiRNAs are small non-coding RNAs that have a large impact on cellular functions by regulating multiple genes simultaneously, and they have been shown to play key roles in skin homeostasis and inflammation. In this commentary to the review article "MicroRNAs in Psoriasis: Immunological Functions and Potential Biomarkers" by Liu et al...
December 19, 2016: Experimental Dermatology
https://www.readbyqxmd.com/read/27982014/monocyte-derived-inflammatory-langerhans-cells-and-dermal-dendritic-cells-mediate-psoriasis-like-inflammation
#12
Tej Pratap Singh, Howard H Zhang, Izabela Borek, Peter Wolf, Michael N Hedrick, Satya P Singh, Brian L Kelsall, Bjorn E Clausen, Joshua M Farber
Dendritic cells (DCs) have been implicated in the pathogenesis of psoriasis but the roles for specific DC subsets are not well defined. Here we show that DCs are required for psoriasis-like changes in mouse skin induced by the local injection of IL-23. However, Flt3L-dependent DCs and resident Langerhans cells are dispensable for the inflammation. In epidermis and dermis, the critical DCs are TNF-producing and IL-1β-producing monocyte-derived DCs, including a population of inflammatory Langerhans cells. Depleting Ly6C(hi) blood monocytes reduces DC accumulation and the skin changes induced either by injecting IL-23 or by application of the TLR7 agonist imiquimod...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27981666/skin-derived-precursors-possess-the-ability-of-differentiation-into-the-epidermal-progeny-and-accelerate-burn-wound-healing
#13
Vahid Bayati, Mohammad Reza Abbaspour, Niloofar Neisi, Mahmoud Hashemitabar
Skin-derived precursors (SKPs) are remnants of the embryonic neural crest stem cells that reside in the dermis until adulthood. Although they possess a wide range of differentiation potentials, their differentiation into keratinocyte-like cells and their roles in skin wound healing are obscure. The present study aimed to investigate the differentiation of SKPs into keratinocyte-like cells and evaluate their role in healing of third degree burn wounds. To this aim, SKPs were differentiated into keratinocyte-like cells on tissue culture plate and collagen-chitosan scaffold prepared by freeze-drying...
December 16, 2016: Cell Biology International
https://www.readbyqxmd.com/read/27978480/adult-nsc-diversity-and-plasticity-the-role-of-the-niche
#14
REVIEW
Enric Llorens-Bobadilla, Ana Martin-Villalba
Adult somatic stem cells are generally defined as cells with the ability to differentiate into multiple different lineages and to self-renew during long periods of time. These features were long presumed to be represented in one single tissue-specific stem cell. Recent development of single-cell technologies reveals the existence of diversity in fate and activation state of somatic stem cells within the blood, skin and intestinal compartments [1] but also in the adult brain. Here we review how recent advances have expanded our view of neural stem cells (NSCs) as a diverse pool of cells and how the specialized microenvironment in which they reside acts to maintain this diversity...
December 12, 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/27973543/intradermal-delivery-of-antigens-enhances-specific-igg-and-diminishes-ige-production-potential-use-for-vaccination-and-allergy-immunotherapy
#15
Takuwa Yasuda, Takehiro Ura, Masaru Taniguchi, Hisahiro Yoshida
Skin is protected by a tough but flexible multilayered barrier and is a front line for immune responses against invading particles. For many years now, skin has been a tissue where certain vaccines are injected for the prevention of infectious disease, however, the detailed mechanisms of the skin immune response are not yet well understood. Using thin and small injection needles, we carefully injected OVA into a restricted region of mouse skin, i.e., intradermal (ID), and examined the antibody response in comparison with subcutaneous (SC) injection or epicutaneous patch administration of OVA...
2016: PloS One
https://www.readbyqxmd.com/read/27964879/activation-of-langerhans-cells-promotes-the-inflammation-in-imiquimod-induced-psoriasis-like-dermatitis
#16
Chunying Xiao, Zhenlai Zhu, Shuhong Sun, Jixin Gao, Meng Fu, Yufeng Liu, Gang Wang, Xu Yao, Wei Li
BACKGROUND: Langerhans cells (LCs) are epidermis-resident dendritic cells that sense and mediate stimuli from skin and outside world, and participate in various skin diseases, playing either pro-inflammatory or regulatory roles. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear, and the conclusions of previous studies are controversial. OBJECTIVES: To explore the role of LCs in mouse model of imiquimod (IMQ)-induced psoriasis-like dermatitis using langerin-diphtheria toxin A (DTA) mice that are constitutively deficient in LCs...
December 5, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27938474/human-muse-cells-non-tumorigenic-pluripotent-like-stem-cells-have-the-capacity-for-liver-regeneration-by-specific-homing-and-replenishment-of-new-hepatocytes-in-liver-fibrosis-mouse-model
#17
Masahiro Iseki, Yoshihiro Kushida, Shohei Wakao, Takahiro Akimoto, Masamichi Mizuma, Fuyuhiko Motoi, Ryuta Asada, Shinobu Shimizu, Michiaki Unno, Gregorio Chazenbalk, Mari Dezawa
Muse cells, a novel type of non-tumorigenic pluripotent-like stem cells reside in the bone marrow, skin and adipose tissue, are collectable as cells positive for pluripotent surface marker SSEA-3. They are able to differentiate into cells representative of all three germ layers. The capacity of intravenously injected human bone marrow-Muse cells to repair the liver fibrosis model of immunodeficient mice was evaluated in this study. They exhibited the ability for differentiation spontaneously into hepatoblast/hepatocyte-lineage cells and high migration toward the serum and liver tissue of carbon tetrachloride-treated mice in vitro...
2, 2016: Cell Transplantation
https://www.readbyqxmd.com/read/27932459/basophil-specific-protease-mmcp-8-provokes-an-inflammatory-response-in-the-skin-with-microvascular-hyperpermeability-and-leukocyte-infiltration
#18
Hidemitsu Tsutsui, Yoshinori Yamanishi, Hiromi Ohtsuka, Shingo Sato, Soichiro Yoshikawa, Hajime Karasuyama
Basophils have often been considered erroneously as minor relatives or blood-circulating precursors of tissue-resident mast cells, because of some phenotypic similarity between them, including basophilic secretory granules in the cytoplasm. However, recent studies revealed that the repertoire of serine proteases stored in secretory granules is distinct between them. Particularly, mouse mast cell protease 8 (mMCP-8) is specifically expressed by basophils but not mast cells in spite of its name. Therefore, mMCP-8 is commonly used as a basophil-specific marker while its functional property remains uncertain...
December 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27927646/bcr-abl-specific-t-cell-therapy-in-ph-all-patients-on-tyrosine-kinase-inhibitors
#19
Patrizia Comoli, Sabrina Basso, Giovanni Riva, Patrizia Barozzi, Ilaria Guido, Antonella Gurrado, Giuseppe Quartuccio, Laura Rubert, Ivana Lagreca, Daniela Vallerini, Fabio Forghieri, Monica Morselli, Paola Bresciani, Angela Cuoghi, Ambra Paolini, Elisabetta Colaci, Roberto Marasca, Antonio Cuneo, Lorenzo Iughetti, Tommaso Trenti, Franco Narni, Robin Foà, Marco Zecca, Mario Luppi, Leonardo Potenza
While the emergence of bone marrow-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome positive, acute lymphoblastic leukemia (Ph+ ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and employing them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease...
December 7, 2016: Blood
https://www.readbyqxmd.com/read/27903738/tgf-%C3%AE-controls-the-formation-of-kidney-resident-t-cells-via-promoting-effector-t-cell-extravasation
#20
Chaoyu Ma, Shruti Mishra, Erika L Demel, Yong Liu, Nu Zhang
Tissue-resident memory T (TRM) cells, a population of noncirculating memory T cells, are one of the essential components of immunological memory in both mouse and human. Although CD69(+)CD103(+) TRM cells represent a major TRM cell population in barrier tissues including the mucosal surface and the skin, CD69(+)CD103(-) TRM cells dominate most nonbarrier tissues, such as the kidney. TGF-β is required for the differentiation of CD69(+)CD103(+) TRM cells in barrier tissues. However, the developmental control of CD69(+)CD103(-) TRM cells in nonbarrier tissues remains largely unknown and the involvement of TGF-β signaling is less clear...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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