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Mucosal Immunology

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https://www.readbyqxmd.com/read/27901018/the-signaling-axis-of-microrna-31-interleukin-25-regulates-th1-th17-mediated-inflammation-response-in-colitis
#1
T Shi, Y Xie, Y Fu, Q Zhou, Z Ma, J Ma, Z Huang, J Zhang, J Chen
Interleukin-25 (IL-25) is an important regulatory cytokine that has a key role on mucosal immune tolerance during inflammation response. However, the molecular mechanism that regulates the colonic IL-25 expression in Crohn's disease (CD) remains unclear. In this study, IL-25 level was proved to decrease in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice and IL-10 knockout (KO) spontaneous colitis mice. An inverse correlation between IL-25 and miR-31 was discovered in the colons from model mice and CD patients...
November 30, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27848953/immunopathogenesis-of-pancreatitis
#2
REVIEW
T Watanabe, M Kudo, W Strober
The conventional view of the pathogenesis of acute and chronic pancreatitis is that it is due to a genetic- or environment-based abnormality of intracellular acinar trypsinogen activation and thus to the induction of acinar cell injury that, in turn, sets in motion an intra-pancreatic inflammatory process. More recent studies, reviewed here, present strong evidence that while such trypsinogen activation is likely a necessary first step in the inflammatory cascade underlying pancreatitis, sustained pancreatic inflammation is dependent on damage-associated molecular patterns-mediated cytokine activation causing the translocation of commensal (gut) organisms into the circulation and their induction of innate immune responses in acinar cells...
November 16, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27848952/crucial-role-of-plasmacytoid-dendritic-cells-in-the-development-of-acute-colitis-through-the-regulation-of-intestinal-inflammation
#3
K Arimura, H Takagi, T Uto, T Fukaya, T Nakamura, N Choijookhuu, Y Hishikawa, Y Yamashita, K Sato
Disruption of intestinal homeostasis can lead to inflammatory bowel diseases endowed susceptibility genes and environmental factors affecting intestinal accumulation and activation of colitogenic phagocytes. Plasmacytoid dendritic cells (pDCs) are immune cells that had been proposed to control innate and adaptive immunity through the massive secretion of type I interferon (IFN-I). However, the contribution of pDCs to the progression of intestinal inflammation remains unclear. Here we show a critical role of pDCs in the initiation of acute colonic inflammation using T-cell-independent acute colitis model with a selective ablation of pDCs...
November 16, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27848951/genetic-deletion-of-the-bacterial-sensor-nod2-improves-murine-crohn-s-disease-like-ileitis-independent-of-functional-dysbiosis
#4
D Corridoni, A Rodriguez-Palacios, G Di Stefano, L Di Martino, D A Antonopoulos, E B Chang, K O Arseneau, T T Pizarro, F Cominelli
Although genetic polymorphisms in NOD2 (nucleotide-binding oligomerization domain-containing 2) have been associated with the pathogenesis of Crohn's disease (CD), little is known regarding the role of wild-type (WT) NOD2 in the gut. To date, most murine studies addressing the role of WT Nod2 have been conducted using healthy (ileitis/colitis-free) mouse strains. Here, we evaluated the effects of Nod2 deletion in a murine model of spontaneous ileitis, i.e., the SAMP1Yit/Fc (SAMP) strain, which closely resembles CD...
November 16, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27848950/the-rectal-mucosa-and-condomless-receptive-anal-intercourse-in-hiv-negative-msm-implications-for-hiv-transmission-and-prevention
#5
C F Kelley, C S Kraft, T Jb de Man, C Duphare, H-W Lee, J Yang, K A Easley, G K Tharp, M J Mulligan, P S Sullivan, S E Bosinger, R R Amara
Most HIV transmissions among men who have sex with men (MSM), the group that accounted for 67% of new US infections in 2014, occur via exposure to the rectal mucosa. However, it is unclear how the act of condomless receptive anal intercourse (CRAI) may alter the mucosal immune environment in HIV-negative MSM. Here, we performed a comprehensive characterization of the rectal mucosal immune environment for the phenotype and production of pro-inflammatory cytokines by CD4 and CD8 T cells, global transcriptomic analyses, and the composition of microbiota in HIV-negative MSM...
November 16, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27827375/predominance-of-weakly-cytotoxic-t-bet-low-eomes-neg-cd8-t-cells-in-human-gastrointestinal-mucosa-implications-for-hiv-infection
#6
B E Kiniry, A Ganesh, J W Critchfield, P W Hunt, F M Hecht, M Somsouk, S G Deeks, B L Shacklett
The gastrointestinal mucosa is an important site of HIV acquisition, viral replication, and pathogenesis. Immune cells in mucosal tissues frequently differ in phenotype and function from their non-mucosal counterparts. Although perforin-mediated cytotoxicity as measured in blood is a recognized correlate of HIV immune control, its role in gastrointestinal tissues is unknown. We sought to elucidate the cytotoxic features of rectal mucosal CD8(+) T-cells in HIV infected and uninfected subjects. Perforin expression and lytic capacity were significantly reduced in rectal CD8(+) T-cells compared with their blood counterparts, regardless of HIV clinical status; granzyme B (GrzB) was reduced to a lesser extent...
November 9, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27827374/microbiota-induces-tonic-ccl2-systemic-levels-that-control-pdc-trafficking-in-steady-state
#7
M Swiecki, H L Miller, R Sesti-Costa, M Cella, S Gilfillan, M Colonna
Plasmacytoid dendritic cells (pDCs) detect viruses initiating antiviral type I interferon responses. The microbiota is known to shape immune responses, but whether it influences pDC homeostasis and/or function is poorly understood. By comparing pDCs in germ-free and specific pathogen-free mice, we found that the microbiota supports homeostatic trafficking by eliciting constitutive levels of the chemokine CCL2 that engages CCR2. Mononuclear phagocytes were required for tonic CCL2 levels. CCL2 was particularly important for trafficking of a CCR2(hi) subset of pDCs that produced proinflammatory cytokines and was prone to apoptosis...
November 9, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27805618/eosinophils-are-required-to-suppress-th2-responses-in-peyer-s-patches-during-intestinal-infection-by-nematodes
#8
J Strandmark, S Steinfelder, C Berek, A A Kühl, S Rausch, S Hartmann
Infections with enteric nematodes result in systemic type 2 helper T (Th2) responses, expansion of immunoglobulin (Ig)G1 antibodies, and eosinophilia. Eosinophils have a supportive role in mucosal Th2 induction during airway hyperreactivity. Whether eosinophils affect the local T-cell and antibody response in the gut-associated lymphoid tissue during enteric infections is unknown. We infected eosinophil-deficient ΔdblGATA-1 mice with the Th2-inducing small intestinal nematode Heligmosomoides polygyrus and found that parasite fecundity was decreased in the absence of eosinophils...
November 2, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27805617/oral-administration-of-a-recombinant-cholera-toxin-b-subunit-promotes-mucosal-healing-in-the-colon
#9
K J Baldauf, J M Royal, J C Kouokam, B Haribabu, V R Jala, K Yaddanapudi, K T Hamorsky, G W Dryden, N Matoba
Cholera toxin B subunit (CTB) is a component of a licensed oral cholera vaccine. However, CTB has pleiotropic immunomodulatory effects whose impacts on the gut are not fully understood. Here, we found that oral administration in mice of a plant-made recombinant CTB (CTBp) significantly increased several immune cell populations in the colon lamina propria. Global gene expression analysis revealed that CTBp had more pronounced impacts on the colon than the small intestine, with significant activation of TGFβ-mediated pathways in the colon epithelium...
November 2, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27782111/inflammatory-cues-enhance-tgf%C3%AE-activation-by-distinct-subsets-of-human-intestinal-dendritic-cells-via-integrin-%C3%AE-v%C3%AE-8
#10
T M Fenton, A Kelly, E E Shuttleworth, C Smedley, A Atakilit, F Powrie, S Campbell, S L Nishimura, D Sheppard, S Levison, J J Worthington, M J Lehtinen, M A Travis
Regulation of intestinal T-cell responses is crucial for immune homeostasis and prevention of inflammatory bowel disease (IBD). A vital cytokine in regulating intestinal T cells is transforming growth factor-β (TGFβ), which is secreted by cells as a latent complex that requires activation to function. However, how TGFβ activation is regulated in the human intestine, and how such pathways are altered in IBD is completely unknown. Here we show that a key activator of TGFβ, integrin αvβ8, is highly expressed on human intestinal dendritic cells (DCs), specifically on the CD1c(+) but not the CD141(+) intestinal DC subset...
October 26, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27759023/mr1-restricted-mucosal-associated-invariant-t-mait-cells-respond-to-mycobacterial-vaccination-and-infection-in-nonhuman-primates
#11
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27759022/a-critical-role-for-irf5-in-regulating-allergic-airway-inflammation
#12
A J Byrne, M Weiss, S A Mathie, S A Walker, H L Eames, D Saliba, C M Lloyd, I A Udalova
Interferon regulatory factor 5 (IRF5) is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection, but its role in regulating pulmonary immune responses to allergen is unknown. We used genetic ablation, adenoviral vector-driven overexpression, and adoptive transfer approaches to interrogate the role of IRF5 in pulmonary immunity and during challenge with the aeroallergen, house dust mite. Global IRF5 deficiency resulted in impaired lung function and extracellular matrix (ECM) deposition...
October 19, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27759021/protection-against-maternal-infection-associated-fetal-growth-restriction-proof-of-concept-with-a-microbial-derived-immunomodulator
#13
N M Scott, J F Lauzon-Joset, A C Jones, K T Mincham, N M Troy, J Leffler, M Serralha, S L Prescott, S A Robertson, C Pasquali, A Bosco, P G Holt, D H Strickland
Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction and/or miscarriage. Treatment strategies for protection of at-risk mothers are limited to a narrow range of vaccines, which do not cover the bulk of the common pathogens most frequently encountered. Using mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), currently used clinically for attenuation of infection-associated airway inflammatory symptoms in infants-adults, markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial lipopolysaccharide or influenza...
October 19, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27731325/gm-csf-produced-by-the-airway-epithelium-is-required-for-sensitization-to-cockroach-allergen
#14
A Sheih, W C Parks, S F Ziegler
Airway epithelial cells are among the first to encounter inhaled allergens and can initiate allergic responses by producing pro-Th2 innate cytokines. In this study, we investigated the role of epithelial-derived cytokines in sensitization to a clinically relevant allergen, cockroach allergen (CRA). Among the epithelial-derived cytokines, granulocyte macrophage colony-stimulating factor (GM-CSF) had a central role in the initiation of Th2 allergic responses to CRA. We show that initial exposure to CRA directly activated airway epithelial cells through a TLR4-MyD88-dependent pathway and MyD88 signaling in epithelial cells induced upregulation of GM-CSF during sensitization...
October 12, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27731324/unique-b7-h1-expression-on-masticatory-mucosae-in-the-oral-cavity-and-trans-coinhibition-by-b7-h1-expressing-keratinocytes-regulating-cd4-t-cell-mediated-mucosal-tissue-inflammation
#15
S Kang, C Zhang, T Ohno, M Azuma
The PD-1/B7-H1 pathway regulates immune responses and maintains homeostasis. Here, we identified a unique expression of B7 homolog 1 (B7-H1) on masticatory mucosae in the oral cavity. B7-H1 was physiologically expressed on the dorsal surface of the tongue, gingiva, and hard palate. Other squamous epithelia and other structures of the epithelia did not express B7-H1 in the steady state. Physiological B7-H1 expression on masticatory mucosae was limited on prickle cells, and its expression on basal keratinocytes (KCs) was strictly regulated...
October 12, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27731323/the-regulatory-dendritic-cell-marker-c1q-is-a-potent-inhibitor-of-allergic-inflammation
#16
L Mascarell, S Airouche, N Berjont, C Gary, C Gueguen, G Fourcade, B Bellier, D Togbe, B Ryffel, D Klatzmann, V Baron-Bodo, P Moingeon
The complement subunit C1q was recently identified as a marker for monocyte-derived regulatory dendritic cells supporting the differentiation of interleukin (IL)-10-secreting CD4(+) T cells with a suppressive activity. Furthermore, C1q expression is upregulated in peripheral blood mononuclear cells of allergic patients in the course of successful allergen immunotherapy. Herein, we investigated a potential direct role of C1q in downregulating allergic inflammation. In mice with ovalbumin (OVA) or birch pollen (BP)-induced allergic asthma, C1q is as efficacious as dexamethasone to reduce both airway hyperresponsiveness (AHR), eosinophil, and ILC2 infiltrates in bronchoalveolar lavages, as well as allergen-specific T helper 2 cells in the lungs...
October 12, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27706128/age-related-spontaneous-lacrimal-keratoconjunctivitis-is-accompanied-by-dysfunctional-t-regulatory-cells
#17
T G Coursey, F Bian, M Zaheer, S C Pflugfelder, E A Volpe, C S de Paiva
In both humans and animal models, the development of Sjögren syndrome (SS) and non-SS keratoconjunctivitis sicca (KCS) increases with age. Here, we investigated the ocular surface and lacrimal gland (LG) phenotype of NOD.B10.H2(b) mice at 7-14, 45-50, and 96-100 weeks. Aged mice develop increased corneal permeability, CD4(+) T-cell infiltration, and conjunctival goblet cell loss. Aged mice have LG atrophy with increased lymphocyte infiltration and inflammatory cytokine levels. An increase in the frequency of CD4(+)Foxp3(+) T regulatory cells (Tregs) was observed with age in the cervical lymph node (CLN), spleen, and LG...
October 5, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27706127/regulatory-t-cells-decrease-invariant-natural-killer-t-cell-mediated-pregnancy-loss-in-mice
#18
L Li, J Tu, Y Jiang, J Zhou, D J Schust
Pregnancy loss is the commonest complication of pregnancy. The causes of pregnancy loss are poorly understood. It has been reported that stimulation of invariant natural killer T (iNKT) cells using α-galactosylceramide (αGC) induces pregnancy loss in mice. Here we investigated the mechanisms, especially the role of regulatory T (Treg) cells, in iNKT cell-mediated pregnancy loss. We found that injection of αGC rapidly induced fetal resorption, activated decidual iNKT cells, decreased the percentage of decidual Treg cells and their interleukin (IL)-10 and transforming growth factor (TGF)-β production, and upregulated the levels of interferon (IFN)-γ, tumor necrosis factor-α, IL-4, and IL-10 in serum...
October 5, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27706126/ror%C3%AE-t-a-multitask-nuclear-receptor-at-mucosal-surfaces
#19
G Eberl
RORγt is a nuclear hormone receptor that has followed an exponential success carrier. Its modest origins as an orphan receptor cloned from human pancreas blossomed within 15 years into a critical regulator of anti-microbial immunity and a major target in the fight against inflammatory pathologies. Here, I review its role as a transcription factor required for the generation of type 3 lymphoid cells, which induce the development of lymphoid tissues, provide resistance of epithelial stem cells to injury, maintain homeostasis with the symbiotic microbiota, orchestrate defense against extracellular microbes, and regulate allergic responses...
October 5, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27677865/the-nasal-mucosal-late-allergic-reaction-to-grass-pollen-involves-type-2-inflammation-il-5-and-il-13-the-inflammasome-il-1%C3%AE-and-complement
#20
B R Leaker, V A Malkov, R Mogg, M K Ruddy, G C Nicholson, A J Tan, C Tribouley, G Chen, I De Lepeleire, N A Calder, H Chung, P Lavender, L N Carayannopoulos, T T Hansel
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1β), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples...
September 28, 2016: Mucosal Immunology
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