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https://www.readbyqxmd.com/read/28214226/cd49a-expression-defines-tissue-resident-cd8-t-cells-poised-for-cytotoxic-function-in-human-skin
#1
Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T Bryceson, Liv Eidsmo
Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8(+) Trm cells on a compartmental and functional basis. In human skin epithelia, CD8(+)CD49a(+) Trm cells produced interferon-γ, whereas CD8(+)CD49a(-) Trm cells produced interleukin-17 (IL-17). In addition, CD8(+)CD49a(+) Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response...
February 13, 2017: Immunity
https://www.readbyqxmd.com/read/28205312/essential-roles-of-tbx3-in-embryonic-skin-development-during-epidermal-stratification
#2
Ryo Ichijo, Yui Iizuka, Hirokazu Kubo, Fumiko Toyoshima
Stepwise differentiation of epidermal cells is essential for development of stratified epithelium, but the underlying mechanisms remain unclear. Here, we show that Tbx3, a member of the T-box family of transcription factors, plays a pivotal role in this mechanism. Tbx3 is expressed in both basal and suprabasal cells in the interfollicular epidermis of mouse embryos. Epidermis-specific Tbx3 conditional knockout (cKO) embryos are small in size and display a thinner epidermis with an impaired barrier function...
February 16, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28199847/neuropilin-1-is-expressed-on-lymphoid-tissue-residing-lti-like-group-3-innate-lymphoid-cells-and-associated-with-ectopic-lymphoid-aggregates
#3
Medya Mara Shikhagaie, Åsa K Björklund, Jenny Mjösberg, Jonas S Erjefält, Anne S Cornelissen, Xavier Romero Ros, Suzanne M Bal, Jasper J Koning, Reina E Mebius, Michiko Mori, Melanie Bruchard, Bianca Blom, Hergen Spits
Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1(+) group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1(+) ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells...
February 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28191777/enhanced-expansion-and-sustained-inductive-function-of-skin-derived-precursor-cells-in-computer-controlled-stirred-suspension-bioreactors
#4
Natacha A Agabalyan, Breanna S Borys, Holly D Sparks, Kathryn Boon, Eko W Raharjo, Sepideh Abbasi, Michael S Kallos, Jeff Biernaskie
Endogenous dermal stem cells (DSCs) reside in the adult hair follicle mesenchyme and can be isolated and grown in vitro as self-renewing colonies called skin-derived precursors (SKPs). Following transplantation into skin, SKPs can generate new dermis and reconstitute the dermal papilla and connective tissue sheath, suggesting they could have important therapeutic value for the treatment of skin disease (alopecia) or injury. Controlled cell culture processes must be developed to efficiently and safely generate sufficient stem cell numbers for clinical use...
February 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28159905/cutting-edge-tissue-resident-memory-t-cells-generated-by-multiple-immunizations-or-localized-deposition-provide-enhanced-immunity
#5
Brooke Davies, Julia E Prier, Claerwen M Jones, Thomas Gebhardt, Francis R Carbone, Laura K Mackay
Tissue-resident memory T cells (TRM) have been shown to afford superior protection against infection, particularly against pathogens that enter via the epithelial surfaces of the body. Although TRM are often concentrated at sites of prior infection, it has been shown that TRM can disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8(+) TRM lodgment in skin. The site of initial T cell priming made little difference to skin lodgement, whereas local inflammation and Ag recognition enhanced TRM accumulation and retention...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28100779/intramembrane-proteolysis-of-astrotactins
#6
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
#7
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...
February 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
#8
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
#9
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
#10
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 and tolerance of skin. VCA tolerance can be established in miniature swine across haploidentical MHC barriers using mixed chimerism. Because the deceased donor pool for VCAs does not permit MHC antigen matching, clinical VCAs are transplanted across varying MHC disparities. We investigated whether sharing of MHC class I or 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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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...
February 2017: Cell Biology International
https://www.readbyqxmd.com/read/27978480/adult-nsc-diversity-and-plasticity-the-role-of-the-niche
#19
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
#20
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
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