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Mucosal Immunology

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https://www.readbyqxmd.com/read/28098247/c-jun-n-terminal-kinase-2-promotes-enterocyte-survival-and-goblet-cell-differentiation-in-the-inflamed-intestine
#1
A D Mandić, E Bennek, J Verdier, K Zhang, S Roubrocks, R J Davis, B Denecke, N Gassler, K Streetz, A Kel, M Hornef, F J Cubero, C Trautwein, G Sellge
c-Jun N-terminal kinases (JNKs) contribute to immune signaling but their functional role during intestinal mucosal inflammation has remained ill defined. Using genetic mouse models, we characterized the role of JNK1 and JNK2 during homeostasis and acute colitis. Epithelial apoptosis, regeneration, differentiation, and barrier function were analyzed in intestinal epithelium-specific (ΔIEC) or complete JNK1 and bone marrow chimeric or complete JNK2 deficient mice as well as double-knockout animals (JNK1(ΔIEC)JNK2(-/-)) during homeostasis and acute dextran sulfate sodium (DSS)-induced colitis...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28098246/tryptophan-metabolite-activation-of-the-aryl-hydrocarbon-receptor-regulates-il-10-receptor-expression-on-intestinal-epithelia
#2
J M Lanis, E E Alexeev, V F Curtis, D A Kitzenberg, D J Kao, K D Battista, M E Gerich, L E Glover, D J Kominsky, S P Colgan
IL-10 is a potent anti-inflammatory cytokine that inhibits the production of proinflammatory mediators. Signaling by IL-10 occurs through the IL-10 receptor (IL-10R), which is expressed in numerous cell types, including intestinal epithelial cells (IECs), where it is associated with development and maintenance of barrier function. Guided by an unbiased metabolomics screen, we identified tryptophan (Trp) metabolism as a major modifying pathway in interferon-γ (IFNγ)-dominant murine colitis. In parallel, we demonstrated that IFNγ induction of indoleamine 2,3-dioxygenase 1, an enzyme that catalyzes the conversion of Trp to kynurenine (Kyn), induces IL-10R1 expression...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28098245/natural-cytotoxicity-receptor-1-in-mouse-unk-cell-maturation-and-function
#3
A M Felker, B A Croy
Early and midgestational decidua of mice genetically ablated for expression of the natural killer (NK) cell natural cytotoxicity receptor (NCR; Ncr1(Gfp/Gfp) mice) shows restricted angiogenesis and atypically small uterine (u)NK cells . We hypothesized that NCR1 inactivation disturbs maturation and angiokine production by uterine natural killer (uNK) cells. Using histological and morphometric approaches, we observed that Ncr1(Gfp/Gfp) but not control C57BL/6 (B6) implantation sites sustain immature, non-granulated uNK cells into midpregnancy...
January 18, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051090/retinoic-acid-takes-effector-t-cells-to-the-gallows-p2x7-the-molecular-hangman
#4
S Das, E J Villablanca
Effector T-cell contraction is one of the primary means by which immune homeostasis in the peripheral tissues is reestablished following an inflammatory response. In this issue of Mucosal Immunology, Hashimoto-Hill et al.(1) show that retinoic acid (RA) transcriptionally upregulates P2X7 primarily in effector T cells of the intestine sensitizing them to NAD-induced cell death (NICD); thus, demonstrating a previously unrecognized role of RA in effector T-cell contraction.Mucosal Immunology advance online publication, 4 January 2017; doi:10...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051089/cadherin-26-is-an-alpha-integrin-binding-epithelial-receptor-regulated-during-allergic-inflammation
#5
J M Caldwell, M H Collins, K A Kemme, J D Sherrill, T Wen, M Rochman, E M Stucke, L Amin, H Tai, P E Putnam, M J Jiménez-Dalmaroni, M R Wormald, A Porollo, J P Abonia, M E Rothenberg
Cadherins (CDH) mediate diverse processes critical in inflammation, including cell adhesion, migration, and differentiation. Herein, we report that the uncharacterized cadherin 26 (CDH26) is highly expressed by epithelial cells in human allergic gastrointestinal tissue. In vitro, CDH26 promotes calcium-dependent cellular adhesion of cells lacking endogenous CDHs by a mechanism involving homotypic binding and interaction with catenin family members (alpha, beta, and p120), as assessed by biochemical assays. Additionally, CDH26 enhances cellular adhesion to recombinant integrin α4β7 in vitro; conversely, recombinant CDH26 binds αE and α4 integrins in biochemical and cellular functional assays, respectively...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051088/lacrimal-gland-derived-il-22-regulates-il-17-mediated-ocular-mucosal-inflammation
#6
Y W Ji, S K Mittal, H S Hwang, E-J Chang, J H Lee, Y Seo, A Yeo, H Noh, H S Lee, S K Chauhan, H K Lee
Inflammatory damage of mucosal surface of the eye is a hallmark of dry eye disease (DED) and, in severe cases, can lead to significant discomfort, visual impairment, and blindness. DED is a multifactorial autoimmune disorder with a largely unknown pathogenesis. Using a cross-sectional patient study and a well-characterized murine model of DED, herein we investigated the immunoregulatory function of interleukin-22 (IL-22) in the pathogenesis of DED. We found that IL-22 levels were elevated in lacrimal fluids of DED patients and inversely correlated with severity of disease...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051087/effects-of-depot-medroxyprogesterone-acetate-on-the-immune-microenvironment-of-the-human-cervix-and-endometrium-implications-for-hiv-susceptibility
#7
K K Smith-McCune, J F Hilton, U Shanmugasundaram, J W Critchfield, R M Greenblatt, D Seidman, S Averbach, L C Giudice, B L Shacklett
Depot-medroxyprogesterone acetate is a commonly used injectable contraceptive that has been associated with an increased risk of HIV acquisition. This study compares effects of depot-medroxyprogesterone acetate on immune parameters from several upper reproductive tract compartments relevant to HIV-1 susceptibility in repetitive samples from 15 depot-medroxyprogesterone acetate users and 27 women not on hormonal contraceptives. Compared with samples from unexposed women in the mid-luteal phase, depot-medroxyprogesterone acetate use was associated with: increased endocervical concentrations of MCP1 and IFNalpha2; decreased endocervical concentrations of IL1beta and IL6; increased proportions of endometrial CD4+ and CD8+ cells expressing the activation marker HLADR; increased density of endometrial macrophages; and decreased density of endometrial regulatory T cells...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051086/neutrophilic-nlrp3-inflammasome-dependent-il-1%C3%AE-secretion-regulates-the-%C3%AE-%C3%AE-t17-cell-response-in-respiratory-bacterial-infections
#8
M Hassane, D Demon, D Soulard, J Fontaine, L E Keller, E C Patin, R Porte, I Prinz, B Ryffel, A Kadioglu, J-W Veening, J-C Sirard, C Faveeuw, M Lamkanfi, F Trottein, C Paget
Traditionally regarded as simple foot soldiers of the innate immune response limited to the eradication of pathogens, neutrophils recently emerged as more complex cells endowed with a set of immunoregulatory functions. Using a model of invasive pneumococcal disease, we highlighted an unexpected key role for neutrophils as accessory cells in innate interleukin (IL)-17A production by lung resident Vγ6Vδ1(+) T cells via nucleotide-binding oligomerization domain receptor, pyrin-containing 3 (NLRP3) inflammasome-dependent IL-1β secretion...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051085/intrinsic-4-1bb-signals-are-indispensable-for-the-establishment-of-an-influenza-specific-tissue-resident-memory-cd8-t-cell-population-in-the-lung
#9
A C Zhou, L E Wagar, M E Wortzman, T H Watts
The induction of long-lived heterotypic T-cell protection against influenza virus remains elusive, despite the conservation of T-cell epitopes. T-cell protection against influenza is critically dependent on lung-resident memory T cells (Trm). Here we show that intranasal administration of 4-1BBL along with influenza nucleoprotein in a replication-defective adenovirus vector to influenza pre-immune mice induces a remarkably stable circulating effector memory CD8 T-cell population characterized by higher IL-7Rα expression than control-boosted T cells, as well as a substantial lung parenchymal CD69(+) CD8 Trm population, including both CD103(+) and CD103(-) cells...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051084/enrichment-of-herpes-simplex-virus-type-2-hsv-2-reactive-mucosal-t-cells-in-the-human-female-genital-tract
#10
C M Posavad, L Zhao, L Dong, L Jin, C E Stevens, A S Magaret, C Johnston, A Wald, J Zhu, L Corey, D M Koelle
Local mucosal cellular immunity is critical in providing protection from HSV-2. To characterize and quantify HSV-2-reactive mucosal T cells, lymphocytes were isolated from endocervical cytobrush and biopsy specimens from 17 HSV-2-infected women and examined ex vivo for the expression of markers associated with maturation and tissue residency and for functional T-cell responses to HSV-2. Compared with their circulating counterparts, cervix-derived CD4+ and CD8+ T cells were predominantly effector memory T cells (CCR7-/CD45RA-) and the majority expressed CD69, a marker of tissue residency...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28051083/the-loss-of-ccr6-and-cd161-cd4-t-cell-homeostasis-contributes-to-disease-progression-in-siv-infected-rhesus-macaques
#11
C S McGary, X Alvarez, S Harrington, B Cervasi, E S Ryan, R I Iriele, S Paganini, J L Harper, K Easley, G Silvestri, A A Ansari, M Lichterfeld, L Micci, M Paiardini
Although previous studies have shown that CD4(+) T cells expressing CCR6 and CD161 are depleted from blood during HIV infection, the mechanisms underlying their loss remain unclear. In this study, we investigated how the homeostasis of CCR6(+) and CD161(+) CD4(+) T cells contributes to SIV disease progression and the mechanisms responsible for their loss from circulation. By comparing SIV infection in rhesus macaques (RMs) and natural host sooty mangabeys (SMs), we found that the loss of CCR6(+) and CD161(+) CD4(+) T cells from circulation is a distinguishing feature of progressive SIV infection in RMs...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28000680/pretreatment-with-antibiotics-may-enhance-the-efficacy-of-fecal-microbiota-transplantation-in-ulcerative-colitis-a-meta-analysis
#12
A H Keshteli, B Millan, K L Madsen
No abstract text is available yet for this article.
December 21, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/28000679/mycobacterium-tuberculosis-cell-wall-released-fragments-by-the-action-of-the-human-lung-mucosa-modulate-macrophages-to-control-infection-in-an-il-10-dependent-manner
#13
J Arcos, S J Sasindran, J I Moliva, J M Scordo, S Sidiki, H Guo, P Venigalla, H V Kelley, G Lin, L Diangelo, S N Silwani, J Zhang, J Turner, J B Torrelles
Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis, is a major public health challenge facing the world. During infection, M.tb is deposited in the lung alveolar space where it comes in contact with the lung mucosa, known as alveolar lining fluid (ALF), an environment that M.tb encounters at different stages of the infection and disease. ALF is abundant in homeostatic and antimicrobial hydrolytic enzymes, also known as hydrolases. Here we demonstrate that ALF hydrolases, at their physiological concentrations and upon contact with M...
December 21, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/28000678/the-effects-of-prebiotics-on-microbial-dysbiosis-butyrate-production-and-immunity-in-hiv-infected-subjects
#14
S Serrano-Villar, J F Vázquez-Castellanos, A Vallejo, A Latorre, T Sainz, S Ferrando-Martínez, D Rojo, J Martínez-Botas, J Del Romero, N Madrid, M Leal, J I Mosele, M J Motilva, C Barbas, M Ferrer, A Moya, S Moreno, M J Gosalbes, V Estrada
Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV(+) viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART(+)) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV(-) controls (HIV(-)), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study...
December 21, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27966557/broadly-neutralizing-antibodies-suppress-post-transcytosis-hiv-1-infectivity
#15
V Lorin, M Malbec, C Eden, T Bruel, F Porrot, M S Seaman, O Schwartz, H Mouquet
Broadly neutralizing antibodies (bNAbs) offer promising opportunities for preventing HIV-1 infection in humans. Immunoprophylaxis with potent bNAbs efficiently protects non-human primates from mucosal transmission even after repeated challenges. However, the precise mechanisms of bNAb-mediated viral inhibition in mucosal tissues are currently unknown. Here, we show that immunoglobulin (Ig)G and IgA bNAbs do not interfere with the endocytic transport of HIV-1 across epithelial cells, a process referred to as transcytosis...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27966556/mv140-a-sublingual-polyvalent-bacterial-preparation-to-treat-recurrent-urinary-tract-infections-licenses-human-dendritic-cells-for-generating-th1-th17-and-il-10-responses-via-syk-and-myd88
#16
C Benito-Villalvilla, C Cirauqui, C M Diez-Rivero, M Casanovas, J L Subiza, O Palomares
Recurrent urinary tract infections (RUTIs) are one of the most common bacterial infectious diseases, especially in women. Antibiotics remain the mainstay of treatment, but their overuse is associated with antibiotic-resistant infections and deleterious effects in the microbiota. Therefore, alternative approaches are fully demanded. Sublingual immunization with MV140 (Uromune), a polyvalent bacterial preparation (PBP) of whole heat-inactivated bacteria, demonstrated clinical efficacy for the treatment of RUTIs, but the involved immunological mechanisms remain unknown...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27966555/reversal-of-trem-1-ectodomain-shedding-and-improved-bacterial-clearance-by-intranasal-metalloproteinase-inhibitors
#17
G Weiss, C Lai, M E Fife, A M Grabiec, B Tildy, R J Snelgrove, G Xin, C M Lloyd, T Hussell
Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27966554/il-36-receptor-deletion-attenuates-lung-injury-and-decreases-mortality-in-murine-influenza-pneumonia
#18
T Aoyagi, M W Newstead, X Zeng, S L Kunkel, M Kaku, T J Standiford
Influenza virus causes a respiratory disease in humans that can progress to lung injury with fatal outcome. The interleukin (IL)-36 cytokines are newly described IL-1 family cytokines that promote inflammatory responses via binding to the IL-36 receptor (IL-36R). The mechanism of expression and the role of IL-36 cytokines are poorly understood. Here, we investigated the role of IL-36 cytokines in modulating the innate inflammatory response during influenza virus-induced pneumonia in mice. The intranasal administration of influenza virus upregulated IL-36α mRNA and protein production in the lungs...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27966553/microbiota-metabolite-short-chain-fatty-acid-acetate-promotes-intestinal-iga-response-to-microbiota-which-is-mediated-by-gpr43
#19
W Wu, M Sun, F Chen, A T Cao, H Liu, Y Zhao, X Huang, Y Xiao, S Yao, Q Zhao, Z Liu, Y Cong
Intestinal IgA, which is regulated by gut microbiota, has a crucial role in maintenance of intestinal homeostasis and in protecting the intestines from inflammation. However, the means by which microbiota promotes intestinal IgA responses remain unclear. Emerging evidence suggests that the host can sense gut bacterial metabolites in addition to pathogen-associated molecular patterns and that recognition of these small molecules influences host immune response in the intestines and beyond. We reported here that microbiota metabolite short-chain fatty acid acetate promoted intestinal IgA responses, which was mediated by "metabolite-sensing" GPR43...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27966552/contraction-of-intestinal-effector-t-cells-by-retinoic-acid-induced-purinergic-receptor-p2x7
#20
S Hashimoto-Hill, L Friesen, M Kim, C H Kim
The intestinal environment harbors a large number of activated T cells, which are potentially inflammatory. To prevent inflammatory responses, intestinal T cells are controlled by various tolerogenic mechanisms, including T-cell apoptosis. We investigated the expression mechanism and function of the purinergic receptor P2X7 in contraction of intestinal CD4(+) effector T cells. We found that P2X7 upregulation on CD4(+) effector T cells is induced by retinoic acid through retinoic acid receptor α binding to an intragenic enhancer region of the P2rx7 gene...
December 14, 2016: Mucosal Immunology
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