Abstract
Deficits in immunological tolerance against self-antigens and antigens provided by the diet and commensal microbiota can result in the development of inflammatory and autoimmune disorders. Dendritic cells (DCs) are pivotal regulators of the immune response, specialized in antigen presentation to drive T cell priming and differentiation. DCs also have a tolerogenic function, participating in the enforcement of central and peripheral tolerance and the resolution of ongoing immune responses. Thus, DCs control effector and regulatory mechanisms relevant to the pathology of autoimmune disorders. In this review, we discuss recent findings regarding the control of the adaptive immune response by tolerogenic DCs. A thorough understanding of the mechanisms that control the tolerogenic DC phenotype will guide the development of novel strategies for the treatment of autoimmunity.
Similar content being viewed by others
References
Josefowicz SZ, Lu LF, Rudensky AY (2012) Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol 30:531–564
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (2011) Pillars article: immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J. Immunol. 1995. J Immunol 186:3808–3821
Fontenot JD, Rasmussen JP, Williams LM, Dooley JL, Farr AG, Rudensky AY, Regulatory T (2005) Cell lineage specification by the forkhead transcription factor foxp3. Immunity 22:329–341
Mucida D, Pino-Lagos K, Kim G, Nowak E, Benson MJ, Kronenberg M, Noelle RJ, Cheroutre H (2009) Retinoic acid can directly promote TGF-beta-mediated Foxp3(+) Treg cell conversion of naive T cells. Immunity 30:471–472 author reply 472-473
Mucida D, Park Y, Kim G, Turovskaya O, Scott I, Kronenberg M, Cheroutre H (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317:256–260
Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A, Ferri E, Salvestrini V, Bonanno G, Rutella S, Durelli I, Horenstein AL, Fiore F, Massaia M, Colombo MP, Baccarani M, Lemoli RM (2007) Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Blood 109:2871–2877
Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK (2001) Type 1 T regulatory cells. Immunol Rev 182:68–79
Groux H, O’Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, Roncarolo MG (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389:737–742
Apetoh L, Quintana FJ, Pot C, Joller N, Xiao S, Kumar D, Burns EJ, Sherr DH, Weiner HL, Kuchroo VK (2010) The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat Immunol 11:854–861
Gandhi R, Kumar D, Burns EJ, Nadeau M, Dake B, Laroni A, Kozoriz D, Weiner HL, Quintana FJ (2010) Activation of the aryl hydrocarbon receptor induces human type 1 regulatory T cell-like and Foxp3(+) regulatory T cells. Nat Immunol 11:846–853
Mascanfroni ID, Takenaka MC, Yeste A, Patel B, Wu Y, Kenison JE, Siddiqui S, Basso AS, Otterbein LE, Pardoll DM, Pan F, Priel A, Clish CB, Robson SC, Quintana FJ (2015) Metabolic control of type 1 regulatory T cell differentiation by AHR and HIF1-alpha. Nat Med 21:638–646
Farez MF, Mascanfroni ID, Mendez-Huergo SP, Yeste A, Murugaiyan G, Garo LP, Aguirre MEB, Patel B, Ysrraelit MC, Zhu C, Kuchroo VK, Rabinovich GA, Quintana FJ, Correale J (2015) Melatonin contributes to the seasonality of multiple sclerosis relapses. Cell 162:1338–1352
Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7:1092–1100
Ohnmacht C, Pullner A, King SB, Drexler I, Meier S, Brocker T, Voehringer D (2009) Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity. J Exp Med 206:549–559
Quintana FJ, Yeste A, Mascanfroni ID (2015) Role and therapeutic value of dendritic cells in central nervous system autoimmunity. Cell Death Differ 22:215–224
Akbari O, DeKruyff RH, Umetsu DT (2001) Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat Immunol 2:725–731
Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS, Keskin DB, Marshall B, Chandler P, Antonia SJ, Burgess R, Slingluff CL Jr, Mellor AL (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870
Travis MA, Reizis B, Melton AC, Masteller E, Tang Q, Proctor JM, Wang Y, Bernstein X, Huang X, Reichardt LF, Bluestone JA, Sheppard D (2007) Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice. Nature 449:361–365
Mascanfroni ID, Yeste A, Vieira SM, Burns EJ, Patel B, Sloma I, Wu Y, Mayo L, Ben-Hamo R, Efroni S, Kuchroo VK, Robson SC, Quintana FJ (2013) IL-27 acts on DCs to suppress the T cell response and autoimmunity by inducing expression of the immunoregulatory molecule CD39. Nat Immunol 14:1054–1063
Mahnke K, Qian Y, Knop J, Enk AH (2003) Induction of CD4+/CD25+ regulatory T cells by targeting of antigens to immature dendritic cells. Blood 101:4862–4869
Onai N, Obata-Onai A, Schmid MA, Ohteki T, Jarrossay D, Manz MG (2007) Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol 8:1207–1216
Naik SH, Sathe P, Park HY, Metcalf D, Proietto AI, Dakic A, Carotta S, O’Keeffe M, Bahlo M, Papenfuss A, Kwak JY, Wu L, Shortman K (2007) Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 8:1217–1226
Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V (2011) Plasmacytoid dendritic cells: recent progress and open questions. Annu Rev Immunol 29:163–183
Merad M, Sathe P, Helft J, Miller J, Mortha A (2013) The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. Annu Rev Immunol 31:563–604
Hacker C, Kirsch RD, Ju XS, Hieronymus T, Gust TC, Kuhl C, Jorgas T, Kurz SM, Rose-John S, Yokota Y, Zenke M (2003) Transcriptional profiling identifies Id2 function in dendritic cell development. Nat Immunol 4:380–386
Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H, Kohyama M, Calderon B, Schraml BU, Unanue ER, Diamond MS, Schreiber RD, Murphy TL, Murphy KM (2008) Batf3 deficiency reveals a critical role for CD8alpha+ dendritic cells in cytotoxic T cell immunity. Science 322:1097–1100
Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, KC W, Albring JC, Satpathy AT, Rotondo JA, Edelson BT, Kretzer NM, Wu X, Weiss LA, Glasmacher E, Li P, Liao W, Behnke M, Lam SS, Aurthur CT, Leonard WJ, Singh H, Stallings CL, Sibley LD, Schreiber RD, Murphy KM (2012) Compensatory dendritic cell development mediated by BATF-IRF interactions. Nature 490:502–507
Park CS, Lee PH, Yamada T, Burns A, Shen Y, Puppi M, Lacorazza HD (2012) Kruppel-like factor 4 (KLF4) promotes the survival of natural killer cells and maintains the number of conventional dendritic cells in the spleen. J Leukoc Biol 91:739–750
Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124:783–801
Yu L, Wang L, Chen S (2010) Endogenous toll-like receptor ligands and their biological significance. J Cell Mol Med 14:2592–2603
Negishi H, Yanai H, Nakajima A, Koshiba R, Atarashi K, Matsuda A, Matsuki K, Miki S, Doi T, Aderem A, Nishio J, Smale ST, Honda K, Taniguchi T (2012) Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nat Immunol 13:659–666
Roses RE, Xu S, Xu M, Koldovsky U, Koski G, Czerniecki BJ (2008) Differential production of IL-23 and IL-12 by myeloid-derived dendritic cells in response to TLR agonists. J Immunol 181:5120–5127
Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV, Steinman RM, Nussenzweig MC (2001) Dendritic cells induce peripheral T cell unresponsiveness under steady state conditions in vivo. J Exp Med 194:769–779
Hawiger D, Masilamani RF, Bettelli E, Kuchroo VK, Nussenzweig MC (2004) Immunological unresponsiveness characterized by increased expression of CD5 on peripheral T cells induced by dendritic cells in vivo. Immunity 20:695–705
Idoyaga J, Fiorese C, Zbytnuik L, Lubkin A, Miller J, Malissen B, Mucida D, Merad M, Steinman RM (2013) Specialized role of migratory dendritic cells in peripheral tolerance induction. J Clin Invest 123:844–854
Ring S, Maas M, Nettelbeck DM, Enk AH, Mahnke K (2013) Targeting of autoantigens to DEC205(+) dendritic cells in vivo suppresses experimental allergic encephalomyelitis in mice. J Immunol 191:2938–2947
Spiering R, Margry B, Keijzer C, Petzold C, Hoek A, Wagenaar-Hilbers J, van der Zee R, van Eden W, Kretschmer K, Broere F (2015) DEC205+ dendritic cell-targeted tolerogenic vaccination promotes immune tolerance in experimental autoimmune arthritis. J Immunol 194:4804–4813
Stern JN, Keskin DB, Kato Z, Waldner H, Schallenberg S, Anderson A, Boehmer H v, Kretschmer K, Strominger JL (2010) Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells. Proc Natl Acad Sci U S A 107:17280–17285
Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19:683–765
Quintana FJ, Sherr DH (2013) Aryl hydrocarbon receptor control of adaptive immunity. Pharmacol Rev 65:1148–1161
Yogev N, Frommer F, Lukas D, Kautz-Neu K, Karram K, Ielo D, Stebut E v, Probst HC, van den Broek M, Riethmacher D, Birnberg T, Blank T, Reizis B, Korn T, Wiendl H, Jung S, Prinz M, Kurschus FC, Waisman A (2012) Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells. Immunity 37:264–275
Zlotnikov-Klionsky Y, Nathansohn-Levi B, Shezen E, Rosen C, Kagan S, Bar-On L, Jung S, Shifrut E, Reich-Zeliger S, Friedman N, Aharoni R, Arnon R, Yifa O, Aronovich A, Reisner Y (2015) , Perforin-positive dendritic cells exhibit an immuno-regulatory role in metabolic syndrome and autoimmunity. Immunity 43:776–787
Zangi L, Klionsky YZ, Yarimi L, Bachar-Lustig E, Eidelstein Y, Shezen E, Hagin D, Ito Y, Takai T, Reich-Zeliger S, Lask A, Milstein O, Jung S, Shinder V, Reisner Y (2012) Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7. Blood 120:1647–1657
Takenaka MC, Quintana FJ (2016) Achieving tolerance with perforin-secreting dendritic cells. Trends Mol Med 22:3–4
Scott CL, Aumeunier AM, Mowat AM (2011) Intestinal CD103+ dendritic cells: master regulators of tolerance? Trends Immunol 32:412–419
Bogunovic M, Ginhoux F, Helft J, Shang L, Hashimoto D, Greter M, Liu K, Jakubzick C, Ingersoll MA, Leboeuf M, Stanley ER, Nussenzweig M, Lira SA, Randolph GJ, Merad M (2009) Origin of the lamina propria dendritic cell network. Immunity 31:513–525
Johansson-Lindbom B, Svensson M, Pabst O, Palmqvist C, Marquez G, Forster R, Agace WW (2005) Functional specialization of gut CD103+ dendritic cells in the regulation of tissue-selective T cell homing. J Exp Med 202:1063–1073
Iwata M, Hirakiyama A, Eshima Y, Kagechika H, Kato C, Song SY (2004) Retinoic acid imprints gut-homing specificity on T cells. Immunity 21:527–538
Sun CM, Hall JA, Blank RB, Bouladoux N, Oukka M, Mora JR, Belkaid Y (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204:1775–1785
Weiner HL, da Cunha AP, Quintana F, Wu H (2011) Oral tolerance. Immunol Rev 241:241–259
Esterházy D, Loschko J, London M, Jove V, Oliveira TY, Mucida D (2016) Classical dendritic cells are required for dietary antigen-mediated induction of peripheral Treg cells and tolerance. Nat Immunol 17:545–555
Muzaki AR, Tetlak P, Sheng J, Loh SC, Setiagani YA, Poidinger M, Zolezzi F, Karjalainen K, Ruedl C (2016) Intestinal CD103(+)CD11b(−) dendritic cells restrain colitis via IFN-γ-induced anti-inflammatory response in epithelial cells. Mucosal Immunol 9:336–351
Klebanoff CA, Spencer SP, Torabi-Parizi P, Grainger JR, Roychoudhuri R, Ji Y, Sukumar M, Muranski P, Scott CD, Hall JA, Ferreyra GA, Leonardi AJ, Borman ZA, Wang J, Palmer DC, Wilhelm C, Cai R, Sun J, Napoli JL, Danner RL, Gattinoni L, Belkaid Y, Restifo NP (2013) Retinoic acid controls the homeostasis of pre-cDC-derived splenic and intestinal dendritic cells. J Exp Med 210:1961–1976
Zelante T, Iannitti RG, Cunha C, De Luca A, Giovannini G, Pieraccini G, Zecchi R, D’Angelo C, Massi-Benedetti C, Fallarino F, Carvalho A, Puccetti P, Romani L (2013) Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. Immunity 39:372–385
Quintana FJ, Murugaiyan G, Farez MF, Mitsdoerffer M, Tukpah AM, Burns EJ, Weiner HL An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 107:20768–20773
Takenaka MC, Araujo LP, Maricato JT, Nascimento VM, Guereschi MG, Rezende RM, Quintana FJ, Basso AS (2016) Norepinephrine controls effector T cell differentiation through β2-adrenergic receptor-mediated inhibition of NF-κB and AP-1 in dendritic cells. J Immunol 196:637–644
Maestroni GJ, Mazzola P (2003) Langerhans cells beta 2-adrenoceptors: role in migration, cytokine production, Th priming and contact hypersensitivity. J Neuroimmunol 144:91–99
Hervé J, Dubreil L, Tardif V, Terme M, Pogu S, Anegon I, Rozec B, Gauthier C, Bach JM, Blancou P (2013) β2-Adrenoreceptor agonist inhibits antigen cross-presentation by dendritic cells. J Immunol 190:3163–3171
Steinbrink K, Wolfl M, Jonuleit H, Knop J, Enk AH (1997) Induction of tolerance by IL-10-treated dendritic cells. J Immunol 159:4772–4780
Takenaka MC, Robson S, Quintana FJ (2016) Regulation of the T Cell Response by CD39. Trends Immunol 37(7):427–439
Macatonia SE, Doherty TM, Knight SC, O’Garra A (1993) Differential effect of IL-10 on dendritic cell-induced T cell proliferation and IFN-gamma production. J Immunol 150:3755–3765
Mitra RS, Judge TA, Nestle FO, Turka LA, Nickoloff BJ (1995) Psoriatic skin-derived dendritic cell function is inhibited by exogenous IL-10. Differential modulation of B7-1 (CD80) and B7-2 (CD86) expression. J Immunol 154:2668–2677
Steinbrink K, Jonuleit H, Müller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. Blood 93:1634–1642
Enk AH, Jonuleit H, Saloga J, Knop J (1997) Dendritic cells as mediators of tumor-induced tolerance in metastatic melanoma. Int J Cancer 73:309–316
Melillo JA, Song L, Bhagat G, Blazquez AB, Plumlee CR, Lee C, Berin C, Reizis B, Schindler C (2010) Dendritic cell (DC)-specific targeting reveals Stat3 as a negative regulator of DC function. J Immunol 184:2638–2645
Nguyen LP, Bradfield CA (2008) The search for endogenous activators of the aryl hydrocarbon receptor. Chem Res Toxicol 21:102–116
McIntosh BE, Hogenesch JB, Bradfield CA (2010) Mammalian Per-Arnt-Sim proteins in environmental adaptation. Annu Rev Physiol 72:625–645
Lo R, Matthews J (2012) High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq. Toxicol Sci 130:349–361
Zhang S, Rowlands C, Safe S (2008) Ligand-dependent interactions of the Ah receptor with coactivators in a mammalian two-hybrid assay. Toxicol Appl Pharmacol 227:196–206
Boronat S, Casado S, Navas JM, Piña B (2007) Modulation of aryl hydrocarbon receptor transactivation by carbaryl, a nonconventional ligand. FEBS J 274:3327–3339
Murray IA, Morales JL, Flaveny CA, Dinatale BC, Chiaro C, Gowdahalli K, Amin S, Perdew GH (2010) Evidence for ligand-mediated selective modulation of aryl hydrocarbon receptor activity. Mol Pharmacol 77:247–254
Matikainen T, Perez GI, Jurisicova A, Pru JK, Schlezinger JJ, Ryu HY, Laine J, Sakai T, Korsmeyer SJ, Casper RF, Sherr DH, Tilly JL (2001) Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals. Nat Genet 28:355–360
Matsumura F (2009) The significance of the nongenomic pathway in mediating inflammatory signaling of the dioxin-activated Ah receptor to cause toxic effects. Biochem Pharmacol 77:608–626
Ohtake F, Baba A, Takada I, Okada M, Iwasaki K, Miki H, Takahashi S, Kouzmenko A, Nohara K, Chiba T, Fujii-Kuriyama Y, Kato S (2007) Dioxin receptor is a ligand-dependent E3 ubiquitin ligase. Nature 446:562–566
Temchura VV, Frericks M, Nacken W, Esser C (2005) Role of the aryl hydrocarbon receptor in thymocyte emigration in vivo. Eur J Immunol 35:2738–2747
Fernandez-Salguero P, Pineau T, Hilbert DM, McPhail T, Lee SS, Kimura S, Nebert DW, Rudikoff S, Ward JM, Gonzalez FJ (1995) Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor. Science 268:722–726
Denison MS, Nagy SR (2003) Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334
Denison MS, Pandini A, Nagy SR, Baldwin EP, Bonati L (2002) Ligand binding and activation of the Ah receptor. Chem Biol Interact 141:3–24
Song J, Clagett-Dame M, Peterson RE, Hahn ME, Westler WM, Sicinski RR, DeLuca HF A ligand for the aryl hydrocarbon receptor isolated from lung. Proc Natl Acad Sci U S A 99:14694–14699
Wei YD, Helleberg H, Rannug U, Rannug A (1998) Rapid and transient induction of CYP1A1 gene expression in human cells by the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. Chem Biol Interact 110:39–55
Moffett JR, Namboodiri MA (2003) Tryptophan and the immune response. Immunol Cell Biol 81:247–265
Nguyen NT, Nakahama T, Le DH, Van Son L, Chu HH, Kishimoto T (2014) Aryl hydrocarbon receptor and kynurenine: recent advances in autoimmune disease research. Front Immunol 5:551
Yeste A, Nadeau M, Burns EJ, Weiner HL, Quintana FJ Nanoparticle-mediated codelivery of myelin antigen and a tolerogenic small molecule suppresses experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 109:11270–11275
Wu HY, Quintana FJ, da Cunha AP, Dake BT, Koeglsperger T, Starossom SC, Weiner HL (2011) In vivo induction of Tr1 cells via mucosal dendritic cells and AHR signaling. PLoS One 6:e23618
Yeste A, Takenaka MC, Mascanfroni ID, Nadeau M, Kenison JE, Patel B, Tukpah AM, Babon JA, DeNicola M, Kent SC, Pozo D, Quintana FJ (2016) Tolerogenic nanoparticles inhibit T cell-mediated autoimmunity through SOCS2. Sci Signal 9:ra61
Tian Y, Ke S, Denison MS, Rabson AB, Gallo MA (1999) Ah receptor and NF-kappa B interactions, a potential mechanism for dioxin toxicity. J Biol Chem 274:510–515
Gillesby BE, Stanostefano M, Porter W, Safe S, Wu ZF, Zacharewski TR (1997) Identification of a motif within the 5’ regulatory region of pS2 which is responsible for AP-1 binding and TCDD-mediated suppression. Biochemistry 36:6080–6089
Vogel CF, Wu D, Goth SR, Baek J, Lollies A, Domhardt R, Grindel A, Pessah IN (2013) Aryl hydrocarbon receptor signaling regulates NF-kappa B RelB activation during dendritic-cell differentiation. Immunol Cell Biol 91:568–575
Vogel CF, Matsumura F (2009) A new cross-talk between the aryl hydrocarbon receptor and RelB, a member of the NF-kappa B family. Biochem Pharmacol 77:734–745
Lee JA, Hwang JA, Sung HN, Jeon CH, Gill BC, Youn HJ, Park JH (2007) 2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates functional differentiation of mouse bone marrow-derived dendritic cells Downregulation of RelB by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Lett 173:31–40
Ruby CE, Leid M, Kerkvliet NI (2002) 2,3,7,8-Tetrachlorodibenzo-p-dioxin suppresses tumor necrosis factor-alpha and anti-CD40-induced activation of NF-kappaB/Rel in dendritic cells: p 50 homodimer activation is not affected. Mol Pharmacol 62:722–728
Benson JM, Shepherd DM (2011) Dietary ligands of the aryl hydrocarbon receptor induce anti-inflammatory and immunoregulatory effects on murine dendritic cells. Toxicol Sci 124:327–338
Hauben E, Gregori S, Draghici E, Migliavacca B, Olivieri S, Woisetschlager M, Roncarolo MG (2008) Activation of the aryl hydrocarbon receptor promotes allograft-specific tolerance through direct and dendritic cell-mediated effects on regulatory T cells. Blood 112:1214–1222
Nguyen NT, Kimura A, Nakahama T, Chinen I, Masuda K, Nohara K, Fujii-Kuriyama Y, Kishimoto T (2010) Aryl hydrocarbon receptor negatively regulates dendritic cell immunogenicity via a kynurenine-dependent mechanism. Proc Natl Acad Sci U S A 107:19961–19966
Mezrich JD, Fechner JH, Zhang X, Johnson BP, Burlingham WJ, Bradfield CA (2010) An interaction between kynurenine and the aryl hydrocarbon receptor can generate regulatory T cells. J Immunol 185:3190–3198
Quintana FJ, Basso AS, Iglesias AH, Korn T, Farez MF, Bettelli E, Caccamo M, Oukka M, Weiner HL (2008) Control of T (reg) and T (H)17 cell differentiation by the aryl hydrocarbon receptor. Nature 453:65–71
Jaronen M, Quintana FJ (2014) Immunological relevance of the coevolution of IDO1 and AHR. Front Immunol 5:521
Acknowledgments
Research in the Quintana laboratory is supported by the National Institutes of Health, the National Multiple Sclerosis Society, the International Progressive MS Alliance, and the American Cancer Society.
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is a contribution to the special issue on Dendritic Cell Subsets and Immune-mediated Diseases - Guest Editor: Francisco Quintana
Rights and permissions
About this article
Cite this article
Takenaka, M.C., Quintana, F.J. Tolerogenic dendritic cells. Semin Immunopathol 39, 113–120 (2017). https://doi.org/10.1007/s00281-016-0587-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00281-016-0587-8