Dendritic cells in intestinal homeostasis and disease.

DCs are specialized APCs that orchestrate innate and adaptive immune responses. The intestinal mucosa contains numerous DCs, which induce either protective immunity to infectious agents or tolerance to innocuous antigens, including food and commensal bacteria. Several subsets of mucosal DCs have been described that display unique functions, dictated in part by the local microenvironment. In this review, we summarize the distinct subtypes of DCs and their distribution in the gut; examine how DC dysfunction contributes to intestinal disease development, including inflammatory bowel disease and celiac disease; and discuss manipulation of DCs for therapy.

[1]  J. Borst,et al.  Blocking CD27-CD70 Costimulatory Pathway Suppresses Experimental Colitis1 , 2009, The Journal of Immunology.

[2]  M. Rescigno,et al.  Intestinal epithelial cells promote colitis-protective regulatory T-cell differentiation through dendritic cell conditioning , 2009, Mucosal Immunology.

[3]  M. Rescigno,et al.  Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells , 2009, Gut.

[4]  G. Corazza,et al.  Increased expression of mucosal addressin cell adhesion molecule 1 in the duodenum of patients with active celiac disease is associated with depletion of integrin alpha4beta7-positive T cells in blood. , 2009, Human pathology.

[5]  Thomas Korn,et al.  IL-17 and Th17 Cells. , 2009, Annual review of immunology.

[6]  B. Lambrecht,et al.  Cyclooxygenase-2 in mucosal DC mediates induction of regulatory T cells in the intestine through suppression of IL-4 , 2009, Mucosal Immunology.

[7]  U. Yrlid,et al.  Steady-state migrating intestinal dendritic cells induce potent inflammatory responses in naive CD4+T cells , 2009, Mucosal Immunology.

[8]  Si-young Song,et al.  GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity , 2009, International immunology.

[9]  D. Cohen,et al.  Suppression of experimental colitis in mice by CD11c+ dendritic cells , 2009, Inflammatory bowel diseases.

[10]  J. Kolls,et al.  Th17 cytokines and mucosal immunity , 2008, Immunological reviews.

[11]  G. Corazza,et al.  Effects of gliadin stimulation on bone marrow-derived dendritic cells from HLA-DQ8 transgenic MICE. , 2008, Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver.

[12]  S. Akira,et al.  Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1β production , 2008, Nature.

[13]  Masahiro Yamamoto,et al.  ATP drives lamina propria TH17 cell differentiation , 2008, Nature.

[14]  A. Gruber,et al.  CD4+Foxp3+ regulatory T cell expansion induced by antigen-driven interaction with intestinal epithelial cells independent of local dendritic cells , 2008, Gut.

[15]  R. Steinman Dendritic cells in vivo: a key target for a new vaccine science. , 2008, Immunity.

[16]  B. Kelsall Recent progress in understanding the phenotype and function of intestinal dendritic cells and macrophages , 2008, Mucosal Immunology.

[17]  F. Powrie,et al.  Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans , 2008, The Journal of experimental medicine.

[18]  R. Kastelein,et al.  Commensal-dependent expression of IL-25 regulates the IL-23–IL-17 axis in the intestine , 2008, The Journal of experimental medicine.

[19]  Keiichiro Suzuki,et al.  Requirement for lymphoid tissue-inducer cells in isolated follicle formation and T cell-independent immunoglobulin A generation in the gut. , 2008, Immunity.

[20]  L. Steinman A rush to judgment on Th17 , 2008, The Journal of experimental medicine.

[21]  Hiroshi Kiyono,et al.  Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5 , 2008, Nature Immunology.

[22]  M. Rescigno,et al.  The biology of intestinal immunoglobulin A responses. , 2008, Immunity.

[23]  C. Coban,et al.  Host innate immune receptors and beyond: making sense of microbial infections. , 2008, Cell host & microbe.

[24]  G. Porro,et al.  Monocyte‐derived dendritic cells from Crohn patients show differential NOD2/CARD15‐dependent immune responses to bacteria , 2008, Inflammatory bowel diseases.

[25]  A. Cerutti The regulation of IgA class switching , 2008, Nature Reviews Immunology.

[26]  F. Powrie,et al.  Dendritic cells in intestinal immune regulation , 2008, Nature Reviews Immunology.

[27]  W. Agace,et al.  IL-10-dependent partial refractoriness to Toll-like receptor stimulation modulates gut mucosal dendritic cell function , 2008, European journal of immunology.

[28]  W. Bemelman,et al.  Dendritic Cell Populations in Colon and Mesenteric Lymph Nodes of Patients With Crohn's Disease , 2008, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[29]  Tomohiro Watanabe,et al.  Muramyl dipeptide activation of nucleotide-binding oligomerization domain 2 protects mice from experimental colitis. , 2008, The Journal of clinical investigation.

[30]  D. Rampton,et al.  Blockade of transforming growth factor β upregulates T-box transcription factor T-bet, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa , 2008, Gut.

[31]  G. Adler,et al.  Commensal Gut Flora Drives the Expansion of Proinflammatory CD4 T Cells in the Colonic Lamina Propria under Normal and Inflammatory Conditions1 , 2008, The Journal of Immunology.

[32]  L. N. Fink,et al.  Epithelial cells prime the immune response to an array of gut‐derived commensals towards a tolerogenic phenotype through distinct actions of thymic stromal lymphopoietin and transforming growth factor‐β , 2007, Immunology.

[33]  D. Schuppan,et al.  In Vitro Differentiation of Human Monocytes into Dendritic Cells by Peptic–Tryptic Digest of Gliadin Is Independent of Genetic Predisposition and the Presence of Celiac Disease , 2008, Journal of Clinical Immunology.

[34]  S. John,et al.  CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages , 2007, Proceedings of the National Academy of Sciences.

[35]  Warren Strober,et al.  The mechanism of action of probiotics , 2007, Current opinion in gastroenterology.

[36]  R. Steinman,et al.  Dendritic cells: Understanding immunogenicity , 2007, European journal of immunology.

[37]  R. Medzhitov,et al.  T helper 17 cells get the NOD. , 2007, Immunity.

[38]  D. Hommes,et al.  Stimulation of the intracellular bacterial sensor NOD2 programs dendritic cells to promote interleukin-17 production in human memory T cells. , 2007, Immunity.

[39]  Steffen Jung,et al.  Conventional dendritic cells regulate the outcome of colonic inflammation independently of T cells , 2007, Proceedings of the National Academy of Sciences.

[40]  G. Corazza,et al.  Evidence for the role of interferon-alfa production by dendritic cells in the Th1 response in celiac disease. , 2007, Gastroenterology.

[41]  H. Ueno,et al.  Dendritic cell subsets in health and disease , 2007, Immunological reviews.

[42]  B. Pulendran,et al.  Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responses , 2007, Nature Immunology.

[43]  M. Rescigno,et al.  The yin and yang of intestinal epithelial cells in controlling dendritic cell function , 2007, The Journal of experimental medicine.

[44]  R. Steinman,et al.  Taking dendritic cells into medicine , 2007, Nature.

[45]  J. Bluestone,et al.  Loss of integrin αvβ8 on dendritic cells causes autoimmunity and colitis in mice , 2007 .

[46]  G. Corazza,et al.  Reduced number and function of peripheral dendritic cells in coeliac disease , 2007, Clinical and experimental immunology.

[47]  Jennifer Louten,et al.  Cutting Edge: Peyer’s Patch Plasmacytoid Dendritic Cells (pDCs) Produce Low Levels of Type I Interferons: Possible Role for IL-10, TGFβ, and Prostaglandin E2 in Conditioning a Unique Mucosal pDC Phenotype1 , 2007, The Journal of Immunology.

[48]  S. Akira,et al.  Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells , 2007, Nature.

[49]  Y. Belkaid,et al.  Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid , 2007, The Journal of experimental medicine.

[50]  Y. Belkaid,et al.  A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism , 2007, The Journal of experimental medicine.

[51]  Hilde Cheroutre,et al.  Reciprocal TH17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid , 2007, Science.

[52]  C. Gianfrani,et al.  Gliadin Regulates the NK-Dendritic Cell Cross-Talk by HLA-E Surface Stabilization1 , 2007, The Journal of Immunology.

[53]  A. Plebani,et al.  Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL. , 2007, Immunity.

[54]  W. Sandborn,et al.  Inflammatory bowel disease: clinical aspects and established and evolving therapies , 2007, The Lancet.

[55]  A. Gruber,et al.  Epithelial-cell-intrinsic IKK-β expression regulates intestinal immune homeostasis , 2007, Nature.

[56]  A. Iwasaki Mucosal dendritic cells. , 2007, Annual review of immunology.

[57]  J. Sirard,et al.  A Key Role of Dendritic Cells in Probiotic Functionality , 2007, PloS one.

[58]  M. Ráki,et al.  Surface Expression of Transglutaminase 2 by Dendritic Cells and its Potential Role for Uptake and Presentation of Gluten Peptides to T Cells , 2007, Scandinavian journal of immunology.

[59]  A. Ding,et al.  Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI , 2007, Nature Immunology.

[60]  R. Steinman,et al.  Dendritic cell–expanded, islet-specific CD4+ CD25+ CD62L+ regulatory T cells restore normoglycemia in diabetic NOD mice , 2007, The Journal of experimental medicine.

[61]  Steffen Jung,et al.  Monocytes give rise to mucosal, but not splenic, conventional dendritic cells , 2007, The Journal of experimental medicine.

[62]  M. Rescigno,et al.  The role of altered microbial signaling via mutant NODs in intestinal inflammation , 2007, Current opinion in gastroenterology.

[63]  J. Bluestone,et al.  Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. , 2007, Nature.

[64]  Thomas Lengauer,et al.  A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1 , 2007, Nature Genetics.

[65]  M. Černá,et al.  Gliadin Peptides Activate Blood Monocytes from Patients with Celiac Disease , 2007, Journal of Clinical Immunology.

[66]  P. Ricciardi-Castagnoli,et al.  Generation of Gut-Homing IgA-Secreting B Cells by Intestinal Dendritic Cells , 2006, Science.

[67]  F. Powrie,et al.  Interleukin-23 drives innate and T cell–mediated intestinal inflammation , 2006, The Journal of experimental medicine.

[68]  R. Toes,et al.  Dendritic cells: vehicles for tolerance induction and prevention of autoimmune diseases. , 2006, Immunobiology.

[69]  H. Link,et al.  Tolerogenic dendritic cells: the ins and outs of outcome. , 2006, Journal of immunotherapy.

[70]  I. Hill The Diagnosis and Treatment of Celiac Disease. , 2006, Gastroenterology & hepatology.

[71]  M. Ráki,et al.  A unique dendritic cell subset accumulates in the celiac lesion and efficiently activates gluten-reactive T cells. , 2006, Gastroenterology.

[72]  I. Williams,et al.  CCR6-mediated dendritic cell activation of pathogen-specific T cells in Peyer's patches. , 2006, Immunity.

[73]  T. Mcclanahan,et al.  IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. , 2006, The Journal of clinical investigation.

[74]  F. Powrie,et al.  Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. , 2006, Immunity.

[75]  A. Šedivá,et al.  Gliadin Fragments Induce Phenotypic and Functional Maturation of Human Dendritic Cells1 , 2005, The Journal of Immunology.

[76]  William W. Agace,et al.  Functional specialization of gut CD103 dendritic cells in the regulation of tissue-selective T cell homing , 2005 .

[77]  F. Powrie,et al.  Essential role for CD103 in the T cell–mediated regulation of experimental colitis , 2005, The Journal of experimental medicine.

[78]  P. Allavena,et al.  Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different. , 2005, Blood.

[79]  M. Albert,et al.  A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. , 2005, Blood.

[80]  H. Radzun,et al.  Increased number of mature dendritic cells in Crohn’s disease: evidence for a chemokine mediated retention mechanism , 2005, Gut.

[81]  M. Kamm,et al.  Characteristics of intestinal dendritic cells in inflammatory bowel diseases. , 2005, Gastroenterology.

[82]  D. Chaplin,et al.  CD70+ antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa , 2005, Nature Immunology.

[83]  G. Corazza,et al.  Coeliac disease , 2005, Journal of Clinical Pathology.

[84]  P. Allavena,et al.  Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells , 2005, Nature Immunology.

[85]  T. Macdonald,et al.  Immunity, Inflammation, and Allergy in the Gut , 2005, Science.

[86]  Hidde L Ploegh,et al.  CX3CR1-Mediated Dendritic Cell Access to the Intestinal Lumen and Bacterial Clearance , 2005, Science.

[87]  A. Scheffold,et al.  Patients with active inflammatory bowel disease lack immature peripheral blood plasmacytoid and myeloid dendritic cells , 2005, Gut.

[88]  J. Orenstein,et al.  Human intestinal macrophages display profound inflammatory anergy despite avid phagocytic and bacteriocidal activity. , 2005, The Journal of clinical investigation.

[89]  P. Kaye,et al.  Stromal cells direct local differentiation of regulatory dendritic cells. , 2004, Immunity.

[90]  G. Trinchieri,et al.  Plasmacytoid dendritic cells in immunity , 2004, Nature Immunology.

[91]  Hua Tang,et al.  Splenic stroma drives mature dendritic cells to differentiate into regulatory dendritic cells , 2004, Nature Immunology.

[92]  H. Kolb,et al.  Wheat Gluten Causes Dendritic Cell Maturation and Chemokine Secretion1 , 2004, The Journal of Immunology.

[93]  J. Bilsborough,et al.  Gastrointestinal dendritic cells play a role in immunity, tolerance, and disease. , 2004, Gastroenterology.

[94]  E. Loftus Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. , 2004, Gastroenterology.

[95]  L. Adorini,et al.  Pharmacological induction of tolerogenic dendritic cells and regulatory T cells. , 2004, Seminars in immunology.

[96]  H. Tilg,et al.  Increased Expression of CCL20 in Human Inflammatory Bowel Disease , 2004, Journal of Clinical Immunology.

[97]  A. Iwasaki,et al.  CD11b+ Peyer’s Patch Dendritic Cells Secrete IL-6 and Induce IgA Secretion from Naive B Cells1 , 2003, The Journal of Immunology.

[98]  M. Neurath,et al.  Constitutive p40 promoter activation and IL-23 production in the terminal ileum mediated by dendritic cells. , 2003, The Journal of clinical investigation.

[99]  V. Raia,et al.  Association between innate response to gliadin and activation of pathogenic T cells in coeliac disease , 2003, The Lancet.

[100]  G. Baretton,et al.  A Subset of Human Dendritic Cells in the T Cell Area of Mucosa-Associated Lymphoid Tissue with a High Potential to Produce TNF-α1 , 2003, The Journal of Immunology.

[101]  F. Powrie,et al.  Cutting Edge: Cure of Colitis by CD4+CD25+ Regulatory T Cells1 , 2003, The Journal of Immunology.

[102]  P. Möller,et al.  Colonic lamina propria dendritic cells in mice with CD4+ T cell‐induced colitis , 2003, European journal of immunology.

[103]  A. Mowat,et al.  Anatomical basis of tolerance and immunity to intestinal antigens , 2003, Nature Reviews Immunology.

[104]  D. Hommes,et al.  Increased expression of DC‐SIGN+IL‐12+IL‐18+ and CD83+IL‐12–IL‐18– dendritic cell populations in the colonic mucosa of patients with Crohn's disease , 2003, European journal of immunology.

[105]  Ranjeny Thomas,et al.  Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. , 2003, Immunity.

[106]  M. Neurath,et al.  Disruption of T helper 2-immune responses in Epstein–Barr virus-induced gene 3-deficient mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[107]  R. Blumberg,et al.  Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. , 2002, Immunity.

[108]  N. Horiike,et al.  Macrophage migration inhibitory factor activates antigen‐presenting dendritic cells and induces inflammatory cytokines in ulcerative colitis , 2002, Clinical and experimental immunology.

[109]  A. Torii,et al.  Differential expression of mucosal addressin cell adhesion molecule‐1 (MAdCAM‐1) in ulcerative colitis and Crohn's disease , 2002, Pathology international.

[110]  T. Honjo,et al.  In situ class switching and differentiation to IgA-producing cells in the gut lamina propria , 2001, Nature.

[111]  P. Möller,et al.  Clustering of Colonic Lamina Propria CD4+ T Cells to Subepithelial Dendritic Cell Aggregates Precedes the Development of Colitis in a Murine Adoptive Transfer Model , 2001, Laboratory Investigation.

[112]  T. Florin,et al.  CD40 and CD86 upregulation with divergent CMRF44 expression on blood dendritic cells in inflammatory bowel diseases , 2001, American Journal of Gastroenterology.

[113]  T. Macdonald,et al.  Interferon‐α drives T cell‐mediated immunopathology in the intestine , 2001, European journal of immunology.

[114]  F. Akbar,et al.  Characterization of antigen-presenting dendritic cells in the peripheral blood and colonic mucosa of patients with ulcerative colitis , 2001, European journal of gastroenterology & hepatology.

[115]  P. Baeuerle,et al.  Phenotype and function of human dendritic cells derived from M‐DC8+ monocytes , 2001, European journal of immunology.

[116]  F. Powrie,et al.  CD134L Expression on Dendritic Cells in the Mesenteric Lymph Nodes Drives Colitis in T Cell-Restored SCID Mice1 , 2001, The Journal of Immunology.

[117]  A. Iwasaki,et al.  Unique Functions of CD11b+, CD8α+, and Double-Negative Peyer’s Patch Dendritic Cells1 , 2001, The Journal of Immunology.

[118]  M. Kamm,et al.  Migration and Maturation of Human Colonic Dendritic Cells , 2001, The Journal of Immunology.

[119]  R. Lorenz,et al.  Spontaneous and Continuous Cyclooxygenase-2-Dependent Prostaglandin E2 Production by Stromal Cells in the Murine Small Intestine Lamina Propria: Directing the Tone of the Intestinal Immune Response1 , 2001, The Journal of Immunology.

[120]  P. Ricciardi-Castagnoli,et al.  Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria , 2001, Nature Immunology.

[121]  Giampiero Girolomoni,et al.  Regulatory Activity of Autocrine IL-10 on Dendritic Cell Functions1 , 2001, The Journal of Immunology.

[122]  A. Iwasaki,et al.  Unique functions of CD11b+, CD8 alpha+, and double-negative Peyer's patch dendritic cells. , 2001, Journal of immunology.

[123]  T. Luger,et al.  Mycophenolate Mofetil Impairs the Maturation and Function of Murine Dendritic Cells1 , 2000, The Journal of Immunology.

[124]  Å. Danielsson,et al.  Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-γδ expression , 2000, Gut.

[125]  L. Adorini,et al.  1α,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation , 2000, The Journal of Immunology.

[126]  F. Huang,et al.  A Discrete Subpopulation of Dendritic Cells Transports Apoptotic Intestinal Epithelial Cells to T Cell Areas of Mesenteric Lymph Nodes , 2000, The Journal of experimental medicine.

[127]  Saul Tzipori,et al.  Biology of , 2021, Evolutionary Biology of Carabus Ground Beetles.

[128]  L. Adorini,et al.  1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. , 2000, Journal of immunology.

[129]  Å. Danielsson,et al.  Characterisation of mucosal lymphoid aggregates in ulcerative colitis: immune cell phenotype and TcR-gammadelta expression. , 2000, Gut.

[130]  C. Elia,et al.  Expression of lymphocyte-endothelial receptor-ligand pairs, α4β7/MAdCAM-1 and OX40/OX40 ligand in the colon and jejunum of patients with inflammatory bowel disease , 1999, Gut.

[131]  D. Mason,et al.  Control of immune pathology by regulatory T cells. , 1998, Current opinion in immunology.

[132]  H. Koeppen,et al.  An interleukin 12-related cytokine is up-regulated in ulcerative colitis but not in Crohn's disease. , 1998, Gastroenterology.

[133]  C. Caux,et al.  Selective Recruitment of Immature and Mature Dendritic Cells by Distinct Chemokines Expressed in Different Anatomic Sites , 1998, The Journal of experimental medicine.

[134]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.