Innate Lymphoid Cells: 10 Years On

Cell, Journal Year: 2018, Volume and Issue: 174(5), P. 1054 - 1066

Published: Aug. 1, 2018

Language: Английский

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The Spectrum and Regulatory Landscape of Intestinal Innate Lymphoid Cells Are Shaped by the Microbiome

Cell, Journal Year: 2016, Volume and Issue: 166(5), P. 1231 - 1246.e13

Published: Aug. 1, 2016

Language: Английский

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S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense

Science, Journal Year: 2018, Volume and Issue: 359(6371), P. 114 - 119

Published: Jan. 5, 2018

Inflammatory ILC2s are itinerant sentinels Group 2 innate lymphoid cells (ILC2s) a population of immune that play important roles in tissue homeostasis and barrier immunity to helminths. Recent work has suggested primarily long-term residents tissues do not readily recirculate. Huang et al. now demonstrate, however, these findings necessarily hold true for the interleukin-25 (IL-25)–responsive KLRG1 hi “inflammatory” ILC2 (iILC2) subset (see Perspective by Mjösberg Rao). In response exogenous IL-25 or helminth infection, iILC2 precursors small intestinal lamina propria proliferate alter their expression sphingosine 1-phosphate (S1P) receptors. They then traffic both lymphatic nonlymphatic organs partly S1P-dependent manner, participating vital anti-helminth repair responses. Science , this issue p. 114 ; see also 36

Language: Английский

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Pulmonary Innate Immune Response Determines the Outcome of Inflammation During Pneumonia and Sepsis-Associated Acute Lung Injury

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 4, 2020

The lung is a primary organ for gas exchange in mammals that represents the largest epithelial surface direct contact with external environment. It also serves as crucial immune organ, which harbors both innate and adaptive cells to induce potent response. Due its outer environment, target many airborne pathogens, toxicants (aerosols), allergens causing pneumonia, acute respiratory distress syndrome (ARDS), injury or inflammation (ALI). current review describes immunological mechanisms responsible bacterial pneumonia sepsis-induced ALI. highlights differences severity of ALI compared pneumonia-associated immune-based between Gram-positive Gram-negative bacteria-induced show different role pulmonary (PECs), alveolar macrophages (AMs), lymphoid (ILCs), pattern-recognition receptors (PRRs, including Toll-like (TLRs) inflammasome proteins) neutrophil infiltration induction have been described during Also, resolution frequently observed associated whereas sepsis-associated lacks it. Hence, mainly response depending on causal pathogen (Gram-positive bacteria) should be taken mind specific therapeutics.

Language: Английский

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NK cells and type 1 innate lymphoid cells: partners in host defense

Nature Immunology, Journal Year: 2016, Volume and Issue: 17(7), P. 758 - 764

Published: June 21, 2016

Language: Английский

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Inflammatory triggers associated with exacerbations of COPD orchestrate plasticity of group 2 innate lymphoid cells in the lungs

Nature Immunology, Journal Year: 2016, Volume and Issue: 17(6), P. 626 - 635

Published: April 25, 2016

Language: Английский

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Mechanisms of allergen immunotherapy for inhaled allergens and predictive biomarkers

Journal of Allergy and Clinical Immunology, Journal Year: 2017, Volume and Issue: 140(6), P. 1485 - 1498

Published: Dec. 1, 2017

Allergen immunotherapy is effective in patients with IgE-dependent allergic rhinitis and asthma. When given continuously for 3 years, there persistent clinical benefit several years after its discontinuation. This disease-modifying effect both antigen-specific antigen-driven. Clinical improvement accompanied by decreases numbers of effector cells target organs, including mast cells, basophils, eosinophils, type 2 innate lymphoid cells. Immunotherapy results the production blocking IgG/IgG4 antibodies that can inhibit activation mediated through high-affinity IgE receptors (FcεRI) on basophils low-affinity (FcεRII) B Suppression TH2 immunity occur as a consequence either deletion or anergy T cells; induction regulatory immune deviation favor TH1 responses. It not clear whether altered long-term memory resides within T-cell B-cell compartment. Recent data highlight role IL-10–producing "protective" likely contribute to tolerance. Understanding mechanisms underlying persistence tolerance should identify predictive biomarkers response discover novel more strategies immunotherapy. GlossaryBet v 1A potent allergen from trees order Fagales, which main cause I allergies observed early spring characterized hay fever, dermatitis, asthma.METHYLATED CpG SITESCpG sites are regions DNA cytosine nucleotide occurs next guanine separated only 1 phosphate. Methylation gene turn off.c-kit (CD117)A cytokine receptor most notably expressed surfaces hematopoietic stem other cell types, CD117 tyrosine kinase III protein binds factor forms dimer activates intrinsic kinase, resulting phosphorylation signal transduction molecules produce signaling.CYTOTOXIC LYMPHOCYTE–ASSOCIATED PROTEIN 4 (CTLA-4)A functions an inhibitory downregulates responses when bound CD80 CD86. CTLA-4 constitutively but upregulated conventional activation.IFN-γA II interferon, IFN-γ required adaptive against viral, bacterial, protozoal infections. has been shown be important activator macrophages inducer class MHC molecule expression. produced predominantly natural killer (NK) NKT part CD4 CD8 cytotoxic lymphocyte once develops.ImmunoCAP (A REGISTERED TRADEMARK OF PHARMACIA DIAGNOSTICS AB)An vitro quantitative assay measures allergen-specific levels human serum. ImmunoCAP assays performed hundreds allergens using cellulose polymer, provides high binding capacity clinically relevant proteins, those present at very low levels.IL-3A growth-promoting capable supporting proliferation broad range basophils.IL-6A also known IFN-β2 implicated wide variety inflammation-associated disease states, IL-6 associated maturation act endogenous pyrogen inducing fever autoimmune diseases infections.IL-12A dendritic macrophages, neutrophils, B-lymphoblastoid (NC-37) antigenic stimulation differentiation naive into cells.IL-21A CD4+ found TH17 subsets follicular induces division/proliferation various system, cells.IL-25A proinflammatory shares sequence similarity IL-17 TH2-type response. IL-25 induce nuclear κB stimulate IL-8 production.IL-33A member IL-1 family cytokines group lymphocytes potently drives TH2-associated cytokines.IL-35An IL-12 regulatory, effector, plays suppression.PROGRAMMED CELL DEATH (PD-1)A cell-surface downregulating system suppressing inflammatory activation. PD-1 checkpoint serves dual promoting apoptosis while simultaneously reducing cells.THYMIC STROMAL LYMPHOPOIETIN (TSLP)A stimulates antigen-presenting such macrophages.TGF-βA secreted many controls proliferation, cellular differentiation, processes regulation differentiation.The Editors wish acknowledge Kristina Bielewicz, MS, preparing this glossary. A off. signaling. develops. An levels. basophils. production. cytokines. suppression. macrophages. differentiation. The Discuss article JACI Journal Club blog: www.jaci-online.blogspot.com. selected rhinitis, mild/moderate asthma.1Burks A.W. Calderon M.A. Casale T. Cox L. Demoly P. Jutel M. et al.Update allergy immunotherapy: American Academy Of Allergy, Asthma & Immunology/European Allergy Immunology/PRACTALL consensus report.J Clin Immunol. 2013; 131: 1288-1296.e3Abstract Full Text PDF PubMed Scopus (247) Google Scholar, 2Bousquet J. Lockey R. Malling H.J. therapeutic vaccines diseases. WHO position paper.J 1998; 102: 558-562Abstract (754) Scholar There heterogeneity populations studied, different products protocols used, outcomes used document efficacy safety.3Dhami S. Nurmatov U. Arasi Khan Asaria Zaman H. al.Allergen rhinoconjunctivitis: systematic review meta-analysis.Allergy. 2017; 72: 1597-1631Crossref (22) Nonetheless, recent guidelines4Roberts G. Pfaar O. Akdis C.A. Ansotegui I.J. Durham S.R. van Wijk R.G. al.EAACI guidelines rhinoconjunctivitis.Allergy. ([Epub head print])Crossref (12) confirm particularly seasonal strongly support use perennial caused house dust mites.5Virchow J.C. Backer V. Kuna Prieto Nolte Villesen H.H. al.Efficacy mite sublingual tablet adults asthma: randomized trial.JAMA. 2016; 315: 1715-1725Crossref (82) Subcutaneous involves weekly updosing injections, followed monthly maintenance injections least years.1Burks 6Durham Walker S.M. Varga E.M. Jacobson M.R. O'Brien F. Noble W. al.Long-term grass-pollen immunotherapy.N Engl J Med. 1999; 341: 468-475Crossref (1061) 7Jutel Jaeger Suck Meyer Fiebig Cromwell Allergen-specific recombinant grass pollen allergens.J 2005; 116: 608-613Abstract (362) In view occasional systemic side effects, subcutaneous requires administration specialist clinic access resuscitative measures. Sublingual daily drops tablets placed under tongue. safer than immunotherapy, it self-administered patient home.1Burks 8Canonica G.W. Pawankar Baena-Cagnani C.E. Blaiss Bonini al.Sublingual World Organization paper 2013 update.World Organ 2014; 7: 6Crossref (205) generally months initiating treatment presesonally/coseasonally short-term benefit. Indirect comparisons have suggested might antiallergic drugs. contrast drugs currently available mAb therapies, routes disease-modifying, manifest remission symptoms discontinuation.9Durham Ying Varney V.A. Sudderick R.M. Mackay I.S. al.Grass inhibits allergen-induced infiltration eosinophils nasal mucosa increases number expressing messenger RNA interferon-gamma.J 1996; 97: 1356-1365Abstract 10Durham Emminger Kapp A. de Monchy J.G. Rak Scadding G.K. al.SQ-standardized confirmation modification trial.J 2012; 129: 717-725.e5Abstract (215) we explore historical inhalant allergens. Our expectation greater understanding will potential could predict and/or monitor treatment. Such knowledge inform new strategies. cardinal features include increased concentrations allergens, local eosinophilia organs. addition regional lymphatic sources IgE, specific synthesized locally respiratory mucosa,11Wu Y.C. James L.K. Vander Heiden J.A. Uduman Kleinstein S.H. al.Influence exposure peripheral blood repertoires rhinitis.J 134: 604-612Abstract (21) thereby accounting phenomenon "local rhinitis" absence detectable serum positive immediate skin test allergens.12Creticos P.S. Peters S.P. Adkinson Jr., N.F. Naclerio Hayes E.C. Norman al.Peptide leukotriene release antigen challenge sensitive ragweed.N 1984; 310: 1626-1630Crossref during (0- 60-minute) provocation. cross-linking adjacent surface triggers seconds minutes preformed mediators, histamine13Naclerio Proud D. Togias A.G. Meyers D.A. Kagey-Sobotka al.Inflammatory mediators late antigen-induced rhinitis.N 1985; 313: 65-70Crossref tryptase,14Castells Schwartz L.B. Tryptase nasal-lavage fluid indicator response.J 1988; 82: 348-355Abstract (0) contained intracytoplasmic granules. Newly formed derived arachidonic acid membrane lipid sulphidopeptide leukotrienes (LTs; LTC4, LTD4, terminal metabolite LTE4),12Creticos platelet-activating factor, prostaglandin D2. biological properties these consistent vasodilatation, edema formation, neurogenic stimulation, mucus secretion characterize typical allergen–induced hypersensitivity. lower airways bronchial smooth muscle contraction, well hypersecretion, acute bronchoconstriction. proportion subjects 10 hours challenge. tissue eosinophilia, congestion, mucosal hyperreactivity nonallergic last days even weeks single findings asthma polyposis, morphologic immunohistochemical airway remodeling feature moderate/severe rhinitis.15Eifan A.O. Orban N.T. Severe rhinitis. inflammation no histologic structural upper remodeling.Am Respir Crit Care 2015; 192: 1431-1439Crossref above pathophysiologic events distinct subset IL-4, key responsible differentiation.16Shamji M.H. Layhadi Cheung D.K. Turka L.A. al.Basophil expression diamine oxidase: biomarker 135: 913-921.e9Abstract (30) 17Eifan Pathogenesis rhinitis.Clin Exp Allergy. 46: 1139-1151Crossref (18) 18Matsuoka Shamji tolerance.Allergol Int. 62: 403-413Abstract (34) IL-4 IL-13 ε-germline transcripts,19Gould Ramadani mouse man memory.Trends 36: 40-48Abstract first step heavy chain rearrangement upregulate vascular adhesion endothelium, 4, integrin α4β1–expressing eosinophils. Both glands airways. IL-5 bone marrow prolongs eosinophil survival inhibiting tissues.20Wechsler M.E. Fulkerson P.C. Bochner B.S. Gauvreau G.M. Gleich G.J. Henkel al.Novel targeted therapies eosinophilic disorders.J 130: 563-571Abstract (62) Along IL-9 cells.21Sehra Yao Nguyen E.T. Glosson-Byers N.L. Akhtar N. Zhou B. al.TH9 accumulation inflammation.J 136: 433-440.e1Abstract (48) Release apparent late-phase 12 challenge.22Durham al.Cytokine IL-3, IL-5, granulocyte/macrophage-colony-stimulating provocation: relationship eosinophilia.J 1992; 148: 2390-2394PubMed Group (ILC2s) represent alternative source mucosa. Innate (ILCs) morphologically similar lymphocytes, although they lineage markers antigen-independent manner.23Spits Cupedo cells: emerging insights development, relationships, function.Annu Rev 30: 647-675Crossref (399) 24Artis Spits biology cells.Nature. 517: 293-301Crossref (403) ILCs consist groups referred ILCs, ILC2s, ILCs. express T-box transcription TNF provide protection intracellular bacteria parasites. ILC2s RAR-related orphan α GATA-3; cytokines, IL-13; helminths, stimulating γt, IL-17a IL-22, afford extracellular bacteria, involved repair processes. was identified cat allergy, who showed ILC2 challenge.25Doherty T.A. Scott Walford Khorram Lund Baum rapidly CD84.J 133: 1203-1205Abstract (37) Subsequently, circulating rhinitis26Lao-Araya Steveling E. Seasonal inhibited immunotherapy.J 1193-1195.e4Abstract asthmatic patients27Lombardi Beuraud C. Neukirch Moussu Morizur Horiot al.Circulating differentially regulated subjects.J 138: 305-308Abstract (9) season. abundant serve amplify maintain TH2-driven inflammation. recently plasticity tissues chronic obstructive pulmonary rhinosinusitis,28Bal Bernink J.H. Nagasawa Groot Shikhagaie M.M. Golebski K. al.IL-1beta, control fate lungs.Nat 17: 636-645Crossref (76) concept must revisited context rhinitis.18Matsuoka Although driven dependent milieu provided interactions between epithelium, (DCs), lymph nodes. atopic subject aeroallergens pass inflamed activated epithelial CCL2 CCL20, recruit immature DCs (Fig 1, A). Activated migrate draining nodes polarize DC migration primed principally Within germinal center node, TH differentiates helper (TFH) TFH IL-21, which, along cell–derived promote immunoglobulin class-switching epithelium expresses IL-25,29Hams Locksley McKenzie A.N. Fallon P.G. Cutting edge: elicits regulate obesity mice.J 191: 5349-5353Crossref (90) IL-33,30Imai Y. Yasuda Sakaguchi Haneda Mizutani Yoshimoto al.Skin-specific IL-33 dermatitis-like mice.Proc Natl Acad Sci U S 110: 13921-13926Crossref (152) thymic stromal lymphopoietin protein.31Kim Siracusa M.C. Saenz S.A. Noti Monticelli Sonnenberg G.F. al.TSLP IL-33-independent inflammation.Sci Transl 5: 170ra16Crossref (273) These development proallergic phenotype32Zimmer Bouley Le Mignon Pliquet Turfkruyer al.A signature correlates 1020-1030Abstract (57) 33Gueguen Luce Duchateau Chamot-Rooke al.Changes driving correlate 137: 545-558Abstract (23) help Additionally, epithelially major growth factors inflammation.34Mjosberg Human cells.J 1265-1276Abstract (25) 35Xue Salimi Panse I. Mjosberg J.M. al.Prostaglandin D2 chemoattractant receptor-homologous 1184-1194Abstract 36Kouser Kappen Walton R.P. Update post immunotherapy.Curr Treat Options 4: 43-53Crossref During subsequent exposure, IgE-facilitated recognition FcεRI FcεRII amplifies inhaled B). DCs, depending their phase, location, milieu, initiate (proallergic DC2s)32Zimmer Scop

Language: Английский

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Mechanisms of Dupilumab

Clinical & Experimental Allergy, Journal Year: 2019, Volume and Issue: 50(1), P. 5 - 14

Published: Sept. 10, 2019

The Th2 cytokines interleukin 4 (IL-4) and IL-13 the heterodimeric IL-4 receptor (IL-4R) complexes that they interact with play a key role in pathogenesis of allergic disorders. Dupilumab is humanized IgG4 monoclonal antibody targets alpha chain (IL-4Rα), common to both IL-4R complexes: type 1 (IL-4Rα/γc; specific) 2 (IL-4Rα/IL-13Rα1; specific). In this review, we detail current state knowledge different signalling pathways coupled examine possible mechanisms action survey its clinical efficacy development widening spectrum applications relevant emphasis on precision medicine approaches blockade involved diseases.

Language: Английский

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The mucosal immune system: master regulator of bidirectional gut–brain communications

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2017, Volume and Issue: 14(3), P. 143 - 159

Published: Jan. 18, 2017

Language: Английский

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Innate lymphoid cells: major players in inflammatory diseases

Nature reviews. Immunology, Journal Year: 2017, Volume and Issue: 17(11), P. 665 - 678

Published: Aug. 14, 2017

Language: Английский

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