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Mucosal Immunology

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https://www.readbyqxmd.com/read/28327619/il-36%C3%AE-signaling-controls-the-induced-regulatory-t-cell-th9-cell-balance-via-nf%C3%AE%C2%BAb-activation-and-stat-transcription-factors
#1
A Harusato, H Abo, V L Ngo, S W Yi, K Mitsutake, S Osuka, J E Kohlmeier, J D Li, A T Gewirtz, A Nusrat, T L Denning
Regulatory and effector T helper (Th) cells are abundant at mucosal surfaces, especially in the intestine, where they control the critical balance between tolerance and inflammation. However, the key factors that reciprocally dictate differentiation along these specific lineages remain incompletely understood. Here we report that the interleukin-1 (IL-1) family member IL-36γ signals through IL-36 receptor, myeloid differentiation primary response gene 88, and nuclear factor-κBp50 in CD4(+) T cells to potently inhibit Foxp3-expressing induced regulatory T cell (Treg) development, while concomitantly promoting the differentiation of Th9 cells via a IL-2-STAT5- (signal transducer and activator of transcription factor 5) and IL-4-STAT6-dependent pathway...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327618/the-transcriptional-repressor-hic1-regulates-intestinal-immune-homeostasis
#2
K Burrows, F Antignano, M Bramhall, A Chenery, S Scheer, V Korinek, T M Underhill, C Zaph
The intestine is a unique immune environment that must respond to infectious organisms but remain tolerant to commensal microbes and food antigens. However, the molecular mechanisms that regulate immune cell function in the intestine remain unclear. Here we identify the POK/ZBTB family transcription factor hypermethylated in cancer 1 (HIC1, ZBTB29) as a central component of immunity and inflammation in the intestine. HIC1 is specifically expressed in immune cells in the intestinal lamina propria (LP) in the steady state and mice with a T-cell-specific deletion of HIC1 have reduced numbers of T cells in the LP...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327617/the-cell-surface-mucin-muc1-limits-the-severity-of-influenza-a-virus-infection
#3
J L McAuley, L Corcilius, H-X Tan, R J Payne, M A McGuckin, L E Brown
Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency...
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28327616/genetic-control-of-autophagy-underlies-pathogenesis-of-inflammatory-bowel-disease
#4
REVIEW
K G Lassen, R J Xavier
Autophagy contributes to cellular homeostasis in the face of nutrient deprivation and other cellular stresses. Cell type-specific functions for autophagy are critical in maintaining homeostasis at both the tissue level and at the whole-organism level. Recent work has highlighted the ways in which human genetic variants modulate autophagy to alter epithelial and immune responses in inflammatory bowel disease.Mucosal Immunology advance online publication 22 March 2017. doi:10.1038/mi.2017.18.
March 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28295020/lactobacillus-johnsonii-supplementation-attenuates-respiratory-viral-infection-via-metabolic-reprogramming-and-immune-cell-modulation
#5
W Fonseca, K Lucey, S Jang, K E Fujimura, A Rasky, H-A Ting, J Petersen, C C Johnson, H A Boushey, E Zoratti, D R Ownby, A M Levine, K R Bobbit, S V Lynch, N W Lukacs
Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28295019/m2e-tetramer-specific-memory-cd4-t-cells-are-broadly-protective-against-influenza-infection
#6
D G Eliasson, A Omokanye, K Schön, U A Wenzel, V Bernasconi, M Bemark, A Kolpe, K El Bakkouri, T Ysenbaert, L Deng, W Fiers, X Saelens, N Lycke
Matrix protein 2 ectodomain (M2e) is considered an attractive component of a broadly protective, universal influenza A vaccine. Here we challenge the canonical view that antibodies against M2e are the prime effectors of protection. Intranasal immunizations of Balb/c mice with CTA1-3M2e-DD-generated M2e-specific memory CD4 T cells that were I-A(d) restricted and critically protected against infection, even in the complete absence of antibodies, as observed in JhD mice. Whereas some M2e-tetramer-specific memory CD4 T cells resided in spleen and lymph nodes, the majority were lung-resident Th17 cells, that rapidly expanded upon a viral challenge infection...
March 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28272393/experimental-vaccine-induces-th1-driven-immune-responses-and-resistance-to-neisseria-gonorrhoeae-infection-in-a-murine-model
#7
Y Liu, L A Hammer, W Liu, M M Hobbs, R A Zielke, A E Sikora, A E Jerse, N K Egilmez, M W Russell
Female mice were immunized intravaginally with gonococcal outer membrane vesicles (OMVs) plus microencapsulated interleukin-12 (IL-12), and challenged using an established model of genital infection with Neisseria gonorrhoeae. Whereas sham-immunized and control animals cleared the infection in 10-13 days, those immunized with OMV plus IL-12 cleared infection with homologous gonococcal strains in 6-9 days. Significant protection was also seen after challenge with antigenically distinct strains of N. gonorrhoeae, and protective anamnestic immunity persisted for at least 6 months after immunization...
March 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28247861/novel-role-for-il-22-in-protection-during-chronic-mycobacterium-tuberculosis-hn878-infection
#8
P Treerat, O Prince, A Cruz-Lagunas, M Muñoz-Torrico, M A Salazar-Lezama, M Selman, B Fallert-Junecko, T A Reinhardt, J F Alcorn, D Kaushal, J Zuñiga, J Rangel-Moreno, J K Kolls, S A Khader
Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces...
March 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28224996/intelectin-contributes-to-allergen-induced-il-25-il-33-and-tslp-expression-and-type-2-response-in-asthma-and-atopic-dermatitis
#9
L Yi, D Cheng, K Zhang, X Huo, Y Mo, H Shi, H Di, Y Zou, H Zhang, J Zhao, Y Xu, D J Erle, G Zhen
The epithelial and epidermal innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) have pivotal roles in the initiation of allergic inflammation in asthma and atopic dermatitis (AD). However, the mechanism by which the expression of these innate cytokines is regulated remains unclear. Intelectin (ITLN) is expressed in airway epithelial cells and promotes allergic airway inflammation. We hypothesized that ITLN is required for allergen-induced IL-25, IL-33, and TSLP expression. In two asthma models, Itln knockdown reduced allergen-induced increases in Il-25, Il-33, and Tslp and development of type 2 response, eosinophilic inflammation, mucus overproduction, and airway hyperresponsiveness...
February 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28224995/genetics-of-eosinophilic-esophagitis
#10
REVIEW
L C Kottyan, M E Rothenberg
Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE...
February 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28198366/th17-cells-express-st2-and-are-controlled-by-the-alarmin-il-33-in-the-small-intestine
#11
A Pascual-Reguant, J Bayat Sarmadi, C Baumann, R Noster, D Cirera-Salinas, C Curato, P Pelczar, S Huber, C E Zielinski, M Löhning, A E Hauser, E Esplugues
TH17 cells are major drivers of inflammation and involved in several autoimmune diseases. Tissue inflammation is a beneficial host response to infection, but it can also contribute to autoimmunity. The crosstalk between a tissue and the immune system during an inflammatory response is key for preserving tissue integrity and restoring physiological processes. However, how the inflamed tissue regulates the magnitude of an immune response by controlling pro-inflammatory T cells is not well characterized so far...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28198365/development-of-conventional-dendritic-cells-from-common-bone-marrow-progenitors-to-multiple-subsets-in-peripheral-tissues
#12
REVIEW
D Sichien, B N Lambrecht, M Guilliams, C L Scott
Our understanding of conventional dendritic cell (cDC) development and the functional specializations of distinct subsets in the peripheral tissues has increased greatly in recent years. Here, we review cDC development from the distinct progenitors in the bone marrow through to the distinct cDC subsets found in barrier tissues, providing an overview of the different subsets described in each location. In addition, we detail the transcription factors and local signals that have been proposed to control this developmental process...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28198364/interleukin-22-drives-nitric-oxide-dependent-dna-damage-and-dysplasia-in-a-murine-model-of-colitis-associated-cancer
#13
C Wang, G Gong, A Sheh, S Muthupalani, E M Bryant, D A Puglisi, H Holcombe, E A Conaway, N A P Parry, V Bakthavatchalu, S P Short, C S Williams, G N Wogan, S R Tannenbaum, J G Fox, B H Horwitz
The risk of colon cancer is increased in patients with Crohn's disease and ulcerative colitis. Inflammation-induced DNA damage could be an important link between inflammation and cancer, although the pathways that link inflammation and DNA damage are incompletely defined. RAG2-deficient mice infected with Helicobacter hepaticus (Hh) develop colitis that progresses to lower bowel cancer. This process depends on nitric oxide (NO), a molecule with known mutagenic potential. We have previously hypothesized that production of NO by macrophages could be essential for Hh-driven carcinogenesis, however, whether Hh infection induces DNA damage in this model and whether this depends on NO has not been determined...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28198363/gut-memories-do-not-fade-epigenetic-regulation-of-lasting-gut-homing-receptor-expression-in-cd4-memory-t-cells
#14
B A Szilagyi, J Triebus, C Kressler, M de Almeida, S Tierling, P Durek, M Mardahl, A Szilagyi, S Floess, J Huehn, U Syrbe, J Walter, J K Polansky, A Hamann
The concept of a "topographical memory" in lymphocytes implies a stable expression of homing receptors mediating trafficking of lymphocytes back to the tissue of initial activation. However, a significant plasticity of the gut-homing receptor α4β7 was found in CD8(+) T cells, questioning the concept. We now demonstrate that α4β7 expression in murine CD4(+) memory T cells is, in contrast, imprinted and remains stable in the absence of the inducing factor retinoic acid (RA) or other stimuli from mucosal environments...
February 15, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28176791/il-36%C3%AE-is-a-crucial-proximal-component-of-protective-type-1-mediated-lung-mucosal-immunity-in-gram-positive-and-negative-bacterial-pneumonia
#15
M A Kovach, B Singer, G Martinez-Colon, M W Newstead, X Zeng, P Mancuso, T A Moore, S L Kunkel, M Peters-Golden, B B Moore, T J Standiford
Interleukin-36γ (IL-36γ) is a member of novel IL-1-like proinflammatory cytokine family that are highly expressed in epithelial tissues and several myeloid-derived cell types. Little is known about the role of the IL-36 family in mucosal immunity, including lung anti-bacterial responses. We used murine models of IL-36γ deficiency to assess the contribution of IL-36γ in the lung during experimental pneumonia. Induction of IL-36γ was observed in the lung in response to Streptococcus pneumoniae (Sp) infection, and mature IL-36γ protein was secreted primarily in microparticles...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28176790/architectural-and-functional-alterations-of-the-small-intestinal-mucosa-in-classical-whipple-s-disease
#16
H-J Epple, J Friebel, V Moos, H Troeger, S M Krug, K Allers, K Schinnerling, A Fromm, B Siegmund, M Fromm, J D Schulzke, T Schneider
Classical Whipple's disease (CWD) affects the gastrointestinal tract and rather elicits regulatory than inflammatory immune reactions. Mechanisms of malabsorption, diarrhea, and systemic immune activation are unknown. We here analyzed mucosal architecture, barrier function, and immune activation as potential diarrheal trigger in specimens from 52 CWD patients. Our data demonstrate villus atrophy and crypt hyperplasia associated with epithelial apoptosis and reduced alkaline phosphatase expression in the duodenum of CWD patients...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28176789/the-intraspecies-diversity-of-c-albicans-triggers-qualitatively-and-temporally-distinct-host-responses-that-determine-the-balance-between-commensalism-and-pathogenicity
#17
F A Schönherr, F Sparber, F R Kirchner, E Guiducci, K Trautwein-Weidner, A Gladiator, N Sertour, U Hetzel, G T T Le, N Pavelka, C d'Enfert, M-E Bougnoux, C F Corti, S LeibundGut-Landmann
The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host...
February 8, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28145442/elevated-gdf-15-contributes-to-pulmonary-inflammation-upon-cigarette-smoke-exposure
#18
F M Verhamme, L J M Seys, E G De Smet, S Provoost, W Janssens, D Elewaut, G F Joos, G G Brusselle, K R Bracke
The molecular mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD) are still unclear, however signaling pathways associated with lung development, such as the transforming growth factor (TGF)-β superfamily, could be implicated in COPD. Growth differentiation factor (GDF)-15, a member of the TGF-β superfamily, is involved in inflammation, mucus secretion, and cachexia. We analyzed the pulmonary expression of GDF-15 in smokers and patients with COPD, in cigarette smoke (CS)-exposed cultures of primary human bronchial epithelial cells (pHBECs), and in CS-exposed mice...
February 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28145441/colonization-with-helicobacter-is-concomitant-with-modified-gut-microbiota-and-drastic-failure-of-the-immune-control-of-mycobacterium-tuberculosis
#19
L Majlessi, F Sayes, J-F Bureau, A Pawlik, V Michel, G Jouvion, M Huerre, M Severgnini, C Consolandi, C Peano, R Brosch, E Touati, C Leclerc
Epidemiological and experimental observations suggest that chronic microbial colonization can impact the immune control of other unrelated pathogens contracted in a concomitant or sequential manner. Possible interactions between Mycobacterium tuberculosis infection and persistence of other bacteria have scarcely been investigated. Here we demonstrated that natural colonization of the digestive tract with Helicobacter hepaticus in mice is concomitant with modification of the gut microbiota, subclinical inflammation, and drastic impairment of immune control of the growth of subsequently administered M...
February 1, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28145440/tissue-specific-differentiation-of-colonic-macrophages-requires-tgf%C3%AE-receptor-mediated-signaling
#20
A Schridde, C C Bain, J U Mayer, J Montgomery, E Pollet, B Denecke, S W F Milling, S J Jenkins, M Dalod, S Henri, B Malissen, O Pabst, A Mcl Mowat
Intestinal macrophages (mφ) form one of the largest populations of mφ in the body and are vital for the maintenance of gut homeostasis. They have several unique properties and are derived from local differentiation of classical Ly6C(hi) monocytes, but the factors driving this tissue-specific process are not understood. Here we have used global transcriptomic analysis to identify a unique homeostatic signature of mature colonic mφ that is acquired as they differentiate in the mucosa. By comparing the analogous monocyte differentiation process found in the dermis, we identify TGFβ as an indispensable part of monocyte differentiation in the intestine and show that it enables mφ to adapt precisely to the requirements of their environment...
February 1, 2017: Mucosal Immunology
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