IL-1 Family Antagonists in Mouse and Human Skin Inflammation

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 16, 2021

Interleukin (IL)-1 family cytokines initiate inflammatory responses, and shape innate adaptive immunity. They play important roles in host defense, but excessive immune activation can also lead to the development of chronic diseases. Dysregulated IL-1 signaling is observed a variety skin disorders. In particular, have been linked pathogenesis psoriasis atopic dermatitis. The biological activity pro-inflammatory agonists controlled by natural receptor antagonists IL-1Ra IL-36Ra, as well regulatory IL-37 IL-38. These four anti-inflammatory members are constitutively highly expressed at steady state epidermis, where keratinocytes major producing cell type. this review, we provide an overview current knowledge concerning their biology inflammation therapeutic potential human We further highlight some common misunderstandings less well-known observations, which persist field despite recent extensive interest for these cytokines.

Language: Английский

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Intestinal mucus barrier: a missing piece of the puzzle in food allergy

Trends in Molecular Medicine, Journal Year: 2021, Volume and Issue: 28(1), P. 36 - 50

Published: Nov. 19, 2021

The sudden rise in food allergy over recent decades has led to various theories including the role of environmental factors sensitization.Gastrointestinal (GI) mucins have recently been implicated maintaining gut homeostasis: mice lacking a functional mucus layer (Muc2−/− mice) are more susceptible colitis and GI infection, addition severe oral tolerance breakdown following sensitization with allergen. Thus, further research will be necessary understand how changes O-glycosylated might contribute epidemic allergy.Factors reduced consumption dietary fiber and/or increased additives emerging as key determinants altered barrier function mucin−gut microbiota interactions which appear play an important regulating allergy. prevalence allergies reached levels but cause remains largely unknown. We discuss clinical relevance mucosal site for allergic food. In this context, we focus on overlooked part pathogenesis, glycoprotein-rich layer, call attention both beneficial detrimental aspects mucus–gut microbiome interactions. Studying intricate links between barrier, associated bacteria, immune system may advance our understanding mechanisms inform prevention treatment strategies Western countries experiencing rising rates without clearly identified [1.Gupta R.S. et al.Prevalence severity among US adults.JAMA Netw. Open. 2019; 2e185630Crossref PubMed Scopus (250) Google Scholar, 2.Lyons S.A. al.Food adults: substantial variation causative foods across Europe.J. Allergy Clin. Immunol. Pract. 7: 1920-1928Abstract Full Text PDF (42) 3.Stephen-Victor E. al.Dietary microbial allergy.Immunity. 2020; 53: 277-289Abstract (10) Scholar], common include peanuts, treenuts, seafood, cow's milk. Food prevalences Europe adults were estimated at 6% 10%, respectively Scholar,2.Lyons Scholar]. allergen (see Glossary) occurs when regulatory responses fail keep up induction allergen-specific proinflammatory [3.Stephen-Victor This drastic increase researchers clinicians propose that modern lifestyles trigger Identifying underlying causually connect is upcoming area would options strategies. can manifest all ages, large spectrum symptoms profiles range from immediate IgE-mediated delayed non-IgE-mediated [4.Connors L. al.Non-IgE-mediated hypersensitivity.Allergy, Asthma 2018; 14: 56Crossref (22) Scholar,5.Anvari S. al.IgE-mediated allergy.Clin. Rev. 57: 244-260Crossref Sensitization allergens initiation disease begin sites share protective features such cohesive epithelium overlies dynamic (Figure 1). Atopic march often refers atopic dermatitis newborn, childhood, asthma persist chronic rhinitis into adulthood [6.Zhu T.H. al.Epithelial dysfunctions dermatitis: skin–gut–lung model linking alteration dysregulation.Br. J. Dermatol. 179: 570-581Crossref (0) Barrier dysfunction leading onset documented context where epithelial disruption triggered by genetics niche-dependent stressors pollutants detergents compromise integrity [7.Sugita K. Kabashima Tight junctions development asthma, rhinosinusitis, dermatitis, eosinophilic esophagitis, inflammatory bowel diseases.J. Leukoc. Biol. 107: 749-762Crossref (18) Scholar,8.Eyerich al.Cutaneous barriers skin immunity: differentiating connected network.Trends 39: 315-327Abstract (78) At surfaces, multiple directly mirror causes other organs tissues lead diseases 1) [9.Kemter A.M. Nagler C.R. Influences through gut, lung, exposures.J. Invest. 129: 1483-1492Crossref (25) here specific understudied component gut: gastrointestinal layer. Mucus crucial feature respiratory digestive tracts [10.Pelaseyed T. al.The goblet cells enterocytes provide first defense line tract interact system.Immunol. 2014; 260: 8-20Crossref (512) 11.Martens E.C. al.Interactions commensal pathogenic microorganisms intestinal barrier.Nat. Microbiol. 16: 457-470Crossref (164) 12.Benam K.H. al.Mucociliary defense: cellular, molecular, animal models.Ann. Am. Thorac. Soc. 15: S210-S215Crossref (9) airways plays similar tract, regulation impaired during state causing pathophysiology [13.Fahy J.V. Dickey B.F. Airway dysfunction.N. Engl. Med. 2010; 363: 2233-2247Crossref (848) mucin glycoproteins building blocks layers, lubricant filtering properties help expulsion luminal contents prevent potential pathogens entering close contact epithelium, while allowing proper absorption digested nutrients mucins, diverse secreted immunological antimicrobial peptides secretory immunoglobulin A (sIgA) potent weapons infections [14.Johansson M.E.V. Hansson G.C. Immunological mucins.Nat. 2016; 639-649Crossref (310) clinically unconnected literature clues about limiting exposure immunologically active residues. An element regulates microbiome, proposed modulator [15.Stefka A.T. al.Commensal bacteria protect against sensitization.Proc. Natl. Acad. Sci. 111: 13145-13150Crossref 16.Feehley al.Healthy infants harbor allergy.Nat. 25: 448-453Crossref (139) 17.Atarashi al.Induction colonic T indigenous Clostridium species.Science. 2011; 331: 337-341Crossref (2288) 18.Renz H. Skevaki C. Early life exposures risks: opportunities prevention.Nat. 2021; 21: 177-191Crossref Hence, parameters influence via activity – habits maturation early-life face developing roles driving affecting [19.Eiwegger al.Recent developments highlights allergy.Allergy Eur. 74: 2355-2367Crossref (29) 20.Venter al.EAACI position paper diet diversity pregnancy, infancy childhood: novel concepts implications studies asthma.Allergy 75: 497-523Crossref (39) 21.Depner M. al.Maturation year contributes farm effect childhood asthma.Nat. 26: 1766-1775Crossref 22.Wesemann D.R. timing, disease.Immunity. 44: 728-738Abstract As broader reviewed elsewhere Scholar,9.Kemter Scholar,22.Wesemann evidence mounting impacts maintenance [23.Desai M.S. al.A fiber-deprived degrades enhances pathogen susceptibility.Cell. 167: 1339-1353Abstract (935) 24.Schroeder B.O. al.Bifidobacteria or protects diet-induced microbiota-mediated deterioration.Cell Host Microbe. 23: 27-40Abstract (246) 25.Earle K.A. al.Quantitative imaging spatial organization.Cell 2015; 18: 478-488Abstract mucus–microbe present perspective functioning layers composed highly (GCs) expand apical surface [26.Javitt G. al.Assembly mechanism von Willebrand factor polymers.Cell. 183: 717-729Abstract (17) organized works exclude microbes remaining permeable essential macromolecules [27.Ermund A. al.Studies mouse stomach, small intestine, colon. I. Gastrointestinal different depending location well Peyer's patches.Am. Physiol. Gastrointest. Liver 2013; 305: G341-G347Crossref (197) Scholar] 2). Moreover, structure composition varies along length parallel morphology mucin-5AC (MUC5AC) predominant gel-forming structured two thick firmly adherent attached overlain loose [28.Atuma gel layer: thickness physical vivo.Am. 2001; 280: G922-G929Crossref These work buffer facilitate proton secretion protecting gastric tissue acidic content [29.Lewis O.L. physics-based pH gradient layer.Am. 2017; 313: G599-G612Crossref (12) intestines, mucin-2 (MUC2) mucin, although structures intestine single permits commensals enter closer these sampled lamina propria antigen-presenting [30.Shan al.Mucus homeostasis delivering immunoregulatory signals.Science. 342: 447-453Crossref (342) By contrast, colon, distinct described, outer being whereas inner one impermeable Scholar,31.Johansson colon MUC2 legislator host-microbial interactions.Proc. U. 108: 4659-4665Crossref (740) Indeed, MUC2-deficient display thinner looser come proximity [32.Wenzel U.A. al.Spontaneous Muc2-deficient reflects cellular ulcerative colitis.PLoS One. 9e100217Crossref (56) reported develop spontaneous even absence [33.Van der Sluis al.Muc2-deficient spontaneously colitis, indicating critical protection.Gastroenterology. 2006; 131: 117-129Abstract (940) Scholar,34.Van Paassen N.B. al.Colitis suckling-weaning transition muc2-deficient mice.Am. 301: G667-G678Crossref (23) addition, they show high susceptibility tumors driven low-grade inflammation proliferative cells, demonstrating preserving [35.Velcich al.Colorectal cancer genetically deficient Muc2.Science. 2002; 295: 1726-1729Crossref (666) Scholar,36.Tadesse al.MUC2 deficiency alters metabolic pathways mucosa.Oncotarget. 8: 71456-71470Crossref protein backbone O-glycosylation viscoelasticity mucus, thus promoting its expel particles, parasites [37.Bergstrom al.Proximal colon-derived encapsulates modulates microbiota.Science. 370: 467-472Crossref Scholar,38.Sharpe sticky end helminths; barrier.Parasite 40e12517Crossref allergens. four main types O-glycan structural cores, terminal fucosylation, sialylation, sulfation, post-translational modifications differentially distributed [11.Martens Scholar,39.Robbe al.Structural distribution O-glycans normal human tract.Biochem. 2004; 384: 307-316Crossref (229) It was shown differential patterning glycosylation proximal distal governs formation two-layered optimal exclusion fecal pellets conformation their proteolysis enzymes [40.Bergstrom al.Core 1- 3-derived collectively maintain mice.Mucosal 10: 91-103Crossref (62) Scholar,41.Van Der Post al.Site-specific inhibits cleavage Porphyromonas gingivalis cysteine protease (RgpB).J. 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Mucin production regulated products described type 2 elicited parasite induce GC hyperplasia IL-13–IL-4Rα–STAT6 pathway [38.Sharpe Scholar,45.Oeser al.Conditional IL-4/IL-13-deficient reveal innate immunity helminths.Mucosal 672-682Crossref cholinergic agonists, histamine prostaglandin E2 released effector inducers intestines [46.Halm Halm S.T. Secretagogue response columnar crypts.Am. Phys. 2000; 278: C212-C233Crossref Scholar,47.Specian R.D. Neutra M.R. Mechanism rapid stimulated acetylcholine.J. Cell 1980; 85: 626-640Crossref Although found allergy, little known subsequent outcome composition. depletion food-allergic patients proctitis [48.Carroccio al.Chronic constipation intolerance: constipation.Scand. Gastroenterol. 2005; 40: 33-42Crossref replenishment observed after avoidance, suggesting allergen-driven contrasts IL-13-driven overproduction pathological [49.Lambrecht B.N. cytokines asthma.Immunity. 50: 975-991Abstract (249) Colonic also (UC, disease, IBD) sentinel entrance crypts do not produce bacterial stimuli, contrast healthy controls remission [50.Van weakening early event pathogenesis.Gut. 68: 2142-2151Crossref (79) revealed UC those exhibit decreased GCs, leaving areas uncovered exposed Studies models demand synthesis leads endoplasmic reticulum (ER) stress apoptosis, turn release [51.Heazlewood C.K. al.Aberrant assembly resembling 2008; 5e54Crossref (493) Scholar,52.Tawiah al.High misfolding stress, reactive oxygen production, apoptosis cells.Am. Pathol. 188: 1354-1373Abstract thought follow discharge induced stimulation inflammation, initiating process remain unclear. helper cell (Th2) cytokines, Th1 Th17 controversial, level regulation. (including etiologically diseases, coexist [53.Virta L.J. al.Cow's milk pediatric IBD.J. Pediatr. Nutr. 56: 649-651Crossref 54.Cai al.Serological investigation G antibodies diseases.PLoS 9e112154Crossref (31) 55.Wasielewska Z. children disease.Postep. Dermatologii i Alergol. 36: 286-294Crossref Children protein-induced enterocolitis (FPIE), endotype allergies, low anti-inflammatory receptor TGFβRI cytokine TNF-α [56.Chung H.L. al.Expression transforming growth β1, I II receptors, mucosa syndrome.J. 109: 150-154Abstract (153) permeability mediate IBD [57.Michielan D'Incà R. Intestinal disease: evaluation, therapy leaky gut.Mediat. Inflamm. 2015: 628517Crossref (243) it together TGF-β signal transduction favor antigen translocation considered affect principally downregulating tight junction proteins, impact studied extensively. pups, TNFRI-dependent manner Muc2 mRNA TNFRII-dependent [58.McElroy S.J. al.Tumor necrosis 1-dependent immature intestine: neonatal necrotizing enterocolitis.Am. 656-666Crossref Scholar]; developed postnatal period. Cytokine-induced ileum emerged TNFRI-mediated secretion, TNFRII-mediated effective mature complexity studying expression, emphasizes need explore levels. mucus-secreting lines, [59.Iwashita al.mRNA

Language: Английский

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Microarray patches enable the development of skin-targeted vaccines against COVID-19

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 171, P. 164 - 186

Published: Feb. 2, 2021

The COVID-19 pandemic is a serious threat to global health and the economy. ongoing race develop safe efficacious vaccine prevent infection by SARS-CoV-2, causative agent for COVID-19, highlights importance of vaccination combat infectious pathogens. highly accessible cutaneous microenvironment an ideal target since skin harbors high density antigen-presenting cells immune accessory with broad innate functions. Microarray patches (MAPs) are attractive intracutaneous biocargo delivery system that enables safe, reproducible, controlled administration components (antigens, or without adjuvants) defined microenvironments. This review describes structure SARS-CoV-2 virus relevant antigenic targets vaccination, summarizes key concepts immunobiology in context prophylactic immunization, presents overview MAP-mediated delivery. Concluding remarks on MAP-based immunization provided contribute rational development effective MAP-delivered vaccines against emerging diseases, including COVID-19.

Language: Английский

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The Gut-Skin Microbiota Axis and Its Role in Diabetic Wound Healing—A Review Based on Current Literature

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(4), P. 2375 - 2375

Published: Feb. 21, 2022

Diabetic foot ulcers (DFU) are a growing concern worldwide as they pose complications in routine clinical practices such diagnosis and management. Bacterial interactions on the skin surface vital to pathophysiology of DFU may control delayed wound healing. The microbiota from our directly regulates cutaneous health disease by interacting with numerous cells involved healing mechanism. Commensal microbiota, particular, interact wound-repairing enhance barrier regeneration. observed microbes include Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, several anaerobes. Skin commensal microbes, namely S. epidermidis, can regulate gamma delta T induce Perforin-2 expression. increased expression destroyed aureus within cells, facilitating Possible crosstalk between human microbiome different cell types promotes immune response helps maintain function humans. Wound is highly well-coordinated, complex mechanism; it be devastating if interrupted. microbiomes being studied relation gut-skin axis along their effects dermatologic conditions. illustrates connection wherein gut impact due its immunological metabolic properties. precise mechanism underlying microbial still unidentified, but endocrine systems likely involved. Next-generation sequencing development bioinformatics pipelines considerably improve understanding microbiome-skin diabetic much more sophisticated way. We endeavor shed light importance these pathways pathomechanisms most prevalent inflammatory conditions including diabetes healing, well how probiotics intervene axis.

Language: Английский

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Spatial transcriptomics landscape of lesions from non-communicable inflammatory skin diseases

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 13, 2022

Abundant heterogeneous immune cells infiltrate lesions in chronic inflammatory diseases and characterization of these is needed to distinguish disease-promoting from bystander cells. Here, we investigate the landscape non-communicable skin (ncISD) by spatial transcriptomics resulting a large repository 62,000 spatially defined human cutaneous transcriptomes 31 patients. Despite expected cell infiltration, observe rather low numbers pathogenic disease promoting cytokine transcripts (IFNG, IL13 IL17A), i.e. >125 times less compared mean expression all other genes over lesional sections. Nevertheless, limited presented disease-specific pattern. Leveraging density-based clustering method, identify specific responder gene signatures direct proximity cytokines, confirm that detected initiate amplification cascades up thousands forming localized epidermal clusters. Thus, within abundant infiltrates ncISD, only number their translated proteins promote initiating an cascade local microenvironment.

Language: Английский

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