Subjects

Abstract

Dendritic cells (DCs) are professional antigen-presenting cells responsible for the activation of specific T-cell responses and for the development of immune tolerance. Immature DCs reside in peripheral tissues and specialize in antigen capture, whereas mature DCs reside mostly in the secondary lymphoid organs where they act as antigen-presenting cells. The correct localization of DCs is strictly regulated by a large variety of chemotactic and nonchemotactic signals that include bacterial products, DAMPs (danger-associated molecular patterns), complement proteins, lipids, and chemokines. These signals function both individually and in concert, generating a complex regulatory network. This network is regulated at multiple levels through different strategies, such as synergistic interactions, proteolytic processing, and the actions of atypical chemokine receptors. Understanding this complex scenario will help to clarify the role of DCs in different pathological conditions, such as autoimmune diseases and cancers and will uncover new molecular targets for therapeutic interventions.

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References

  1. 1.

    Steinman, R. M. Decisions about dendritic cells: past, present, and future. Annu. Rev. Immunol. 30, 1–22 (2012).

  2. 2.

    Banchereau, J. & Steinman, R. M. Dendritic cells and the control of immunity. Nature 392, 245–252 (1998).

  3. 3.

    Murphy, T. L. et al. Transcriptional control of dendritic cell development. Annu. Rev. Immunol. 34, 93–119 (2016).

  4. 4.

    Randolph, G. J., Ochando, J. & Partida-Sanchez, S. Migration of dendritic cell subsets and their precursors. Annu. Rev. Immunol. 26, 293–316 (2008).

  5. 5.

    Durai, V. & Murphy, K. M. Functions of murine dendritic cells. Immunity 45, 719–736 (2016).

  6. 6.

    Briseno, C. G., Murphy, T. L. & Murphy, K. M. Complementary diversification of dendritic cells and innate lymphoid cells. Curr. Opin. Immunol. 29, 69–78 (2014).

  7. 7.

    Itano, A. A. & Jenkins, M. K. Antigen presentation to naive CD4 T cells in the lymph node. Nat. Immunol. 4, 733–739 (2003).

  8. 8.

    Lanzavecchia, A. & Sallusto, F. The instructive role of dendritic cells on T cell responses: lineages, plasticity and kinetics. Curr. Opin. Immunol. 13, 291–298 (2001).

  9. 9.

    Del Prete, A. et al. Migration of dendritic cells across blood and lymphatic endothelial barriers. Thromb. Haemost. 95, 22–28 (2006).

  10. 10.

    Ohl, L. et al. CCR7 governs skin dendritic cell migration under inflammatory and steady-state conditions. Immunity 21, 279–288 (2004).

  11. 11.

    Sozzani, S. Dendritic cell trafficking: more than just chemokines. Cytokine Growth Factor. Rev. 16, 581–592 (2005).

  12. 12.

    Lukacs-Kornek, V., Engel, D., Tacke, F. & Kurts, C. The role of chemokines and their receptors in dendritic cell biology. Front. Biosci. 13, 2238–2252 (2008).

  13. 13.

    Bachelerie, F. et al. An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15. Br. J. Pharmacol. 172, 3945–3949 (2015).

  14. 14.

    Griffith, J. W., Sokol, C. L. & Luster, A. D. Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol. 32, 659–702 (2014).

  15. 15.

    Mantovani, A., Locati, M., Vecchi, A., Sozzani, S. & Allavena, P. Decoy receptors: a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol. 22, 328–336 (2001).

  16. 16.

    Bonecchi, R. & Graham, G. J. Atypical chemokine receptors and their roles in the resolution of the inflammatory response. Front. Immunol. 7, 224 (2016).

  17. 17.

    Nibbs, R. J. & Graham, G. J. Immune regulation by atypical chemokine receptors. Nat. Rev. Immunol. 13, 815–829 (2013).

  18. 18.

    Sozzani, S., Vermi, W., Del Prete, A. & Facchetti, F. Trafficking properties of plasmacytoid dendritic cells in health and disease. Trends Immunol. 31, 270–277 (2010).

  19. 19.

    Yun, T. J. et al. Indoleamine 2,3-dioxygenase-expressing aortic plasmacytoid dendritic cells protect against atherosclerosis by induction of regulatory T cells. Cell. Metab. 23, 852–866 (2016).

  20. 20.

    Sozzani, S. et al. Differential regulation of chemokine receptors during dendritic cell maturation: a model for their trafficking properties. J. Immunol. 161, 1083–1086 (1998).

  21. 21.

    Nakano, H., Lyons-Cohen, M. R., Whitehead, G. S., Nakano, K. & Cook, D. N. Distinct functions of CXCR4, CCR2, and CX3CR1 direct dendritic cell precursors from the bone marrow to the lung. J. Leukoc. Biol. 101, 1143–1153 (2017).

  22. 22.

    Tassone, L. et al. Defect of plasmacytoid dendritic cells in warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome patients. Blood 116, 4870–4873 (2010).

  23. 23.

    Clausen, B. E. & Stoitzner, P. Functional specialization of skin dendritic cell subsets in regulating T cell responses. Front. Immunol. 6, 534 (2015).

  24. 24.

    Braun, A. et al. Afferent lymph-derived T cells and DCs use different chemokine receptor CCR7-dependent routes for entry into the lymph node and intranodal migration. Nat. Immunol. 12, 879–887 (2011).

  25. 25.

    Lian, J. & Luster, A. D. Chemokine-guided cell positioning in the lymph node orchestrates the generation of adaptive immune responses. Curr. Opin. Cell. Biol. 36, 1–6 (2015).

  26. 26.

    Johnson, L. A. & Jackson, D. G. Inflammation-induced secretion of CCL21 in lymphatic endothelium is a key regulator of integrin-mediated dendritic cell transmigration. Int. Immunol. 22, 839–849 (2010).

  27. 27.

    Vaahtomeri, K. et al. Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Cell Rep. 19, 902–909 (2017).

  28. 28.

    Weber, M. et al. Interstitial dendritic cell guidance by haptotactic chemokine gradients. Science 339, 328–332 (2013).

  29. 29.

    Tal, O. et al. DC mobilization from the skin requires docking to immobilized CCL21 on lymphatic endothelium and intralymphatic crawling. J. Exp. Med. 208, 2141–2153 (2011).

  30. 30.

    MartIn-Fontecha, A. et al. Regulation of dendritic cell migration to the draining lymph node: impact on T lymphocyte traffic and priming. J. Exp. Med. 198, 615–621 (2003).

  31. 31.

    Del Prete, A. et al. Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function. Blood 109, 626–631 (2007).

  32. 32.

    Middel, P., Raddatz, D., Gunawan, B., Haller, F. & Radzun, H. J. Increased number of mature dendritic cells in Crohn’s disease: evidence for a chemokine mediated retention mechanism. Gut 55, 220–227 (2006).

  33. 33.

    Schumann, K. et al. Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells. Immunity 32, 703–713 (2010).

  34. 34.

    Bryce, S. A. et al. ACKR4 on stromal cells scavenges CCL19 to enable CCR7-dependent trafficking of APCs from inflamed skin to lymph nodes. J. Immunol. 196, 3341–3353 (2016).

  35. 35.

    Ulvmar, M. H. et al. The atypical chemokine receptor CCRL1 shapes functional CCL21 gradients in lymph nodes. Nat. Immunol. 15, 623–630 (2014).

  36. 36.

    Leventhal, D. S. et al. Dendritic cells coordinate the development and homeostasis of organ-specific regulatory T cells. Immunity 44, 847–859 (2016).

  37. 37.

    Johnson, L. A. & Jackson, D. G. The chemokine CX3CL1 promotes trafficking of dendritic cells through inflamed lymphatics. J. Cell. Sci. 126, 5259–5270 (2013).

  38. 38.

    Kabashima, K. et al. CXCL12-CXCR4 engagement is required for migration of cutaneous dendritic cells. Am. J. Pathol. 171, 1249–1257 (2007).

  39. 39.

    Stutte, S. et al. Requirement of CCL17 for CCR7- and CXCR4-dependent migration of cutaneous dendritic cells. Proc. Natl Acad. Sci. Usa. 107, 8736–8741 (2010).

  40. 40.

    Ruland C. et al. Chemokine CCL17 is expressed by dendritic cells in the CNS during experimental autoimmune encephalomyelitis and promotes pathogenesis of disease. Brain Behav Immun. 66, 382–393 (2017).

  41. 41.

    Gouwy, M., Struyf, S., Catusse, J., Proost, P. & Van Damme, J. Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration. J. Leukoc. Biol. 76, 185–194 (2004).

  42. 42.

    Gouwy, M. et al. Chemokines and other GPCR ligands synergize in receptor-mediated migration of monocyte-derived immature and mature dendritic cells. Immunobiology 219, 218–229 (2014).

  43. 43.

    Sebastiani, S., Danelon, G., Gerber, B. & Uguccioni, M. CCL22-induced responses are powerfully enhanced by synergy inducing chemokines via CCR4: evidence for the involvement of first beta-strand of chemokine. Eur. J. Immunol. 35, 746–756 (2005).

  44. 44.

    Panzer, U. & Uguccioni, M. Prostaglandin E2 modulates the functional responsiveness of human monocytes to chemokines. Eur. J. Immunol. 34, 3682–3689 (2004).

  45. 45.

    Sadik, C. D. & Luster, A. D. Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. J. Leukoc. Biol. 91, 207–215 (2012).

  46. 46.

    Sozzani, S. et al. Synergism between platelet activating factor and C-C chemokines for arachidonate release in human monocytes. Biochem. Biophys. Res. Commun. 199, 761–766 (1994).

  47. 47.

    Penna, G., Sozzani, S. & Adorini, L. Cutting edge: selective usage of chemokine receptors by plasmacytoid dendritic cells. J. Immunol. 167, 1862–1866 (2001).

  48. 48.

    Krug, A. et al. IFN-producing cells respond to CXCR3 ligands in the presence of CXCL12 and secrete inflammatory chemokines upon activation. J. Immunol. 169, 6079–6083 (2002).

  49. 49.

    Bai, Z. et al. CXC chemokine ligand 12 promotes CCR7-dependent naive T cell trafficking to lymph nodes and Peyer’s patches. J. Immunol. 182, 1287–1295 (2009).

  50. 50.

    Umemoto, E. et al. Constitutive plasmacytoid dendritic cell migration to the splenic white pulp is cooperatively regulated by CCR7- and CXCR4-mediated signaling. J. Immunol. 189, 191–199 (2012).

  51. 51.

    Cecchinato, V., D’Agostino, G., Raeli, L. & Uguccioni, M. Chemokine interaction with synergy-inducing molecules: fine tuning modulation of cell trafficking. J. Leukoc. Biol. 99, 851–855 (2016).

  52. 52.

    Mellado, M. et al. Chemokine receptor homo- or heterodimerization activates distinct signaling pathways. Embo. J. 20, 2497–2507 (2001).

  53. 53.

    Majumdar, R., Sixt, M. & Parent, C. A. New paradigms in the establishment and maintenance of gradients during directed cell migration. Curr. Opin. Cell. Biol. 30, 33–40 (2014).

  54. 54.

    Sozzani, S. & Del Prete, A. Chemokines as relay signals in human dendritic cell migration: serum amyloid A kicks off chemotaxis. Eur. J. Immunol. 45, 40–43 (2015).

  55. 55.

    Chou, R. C. et al. Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis. Immunity 33, 266–278 (2010).

  56. 56.

    Lammermann, T. et al. Neutrophil swarms require LTB4 and integrins at sites of cell death in vivo. Nature 498, 371–375 (2013).

  57. 57.

    Chen, K. et al. Signal relay by CC chemokine receptor 2 (CCR2) and formylpeptide receptor 2 (Fpr2) in the recruitment of monocyte-derived dendritic cells in allergic airway inflammation. J. Biol. Chem. 288, 16262–16273 (2013).

  58. 58.

    Salogni, L. et al. Activin A induces dendritic cell migration through the polarized release of CXC chemokine ligands 12 and 14. Blood 113, 5848–5856 (2009).

  59. 59.

    Gouwy, M. et al. Serum amyloid A chemoattracts immature dendritic cells and indirectly provokes monocyte chemotaxis by induction of cooperating CC and CXC chemokines. Eur. J. Immunol. 45, 101–112 (2015).

  60. 60.

    Hjorto, G. M. et al. Differential CCR7 targeting in dendritic cells by three naturally occurring CC-chemokines. Front. Immunol. 7, 568 (2016).

  61. 61.

    Bachelerie, F. et al. International union of basic and clinical pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol. Rev. 66, 1–79 (2014).

  62. 62.

    Bachelerie, F. et al. New nomenclature for atypical chemokine receptors. Nat. Immunol. 15, 207–208 (2014).

  63. 63.

    McKimmie, C. S. et al. An analysis of the function and expression of D6 on lymphatic endothelial cells. Blood 121, 3768–3777 (2013).

  64. 64.

    Liu, L. et al. Cutting edge: the silent chemokine receptor D6 is required for generating T-cell responses that mediate experimental autoimmune encephalomyelitis. J. Immunol. 177, 17–21 (2006).

  65. 65.

    Hansell, C. A. et al. The atypical chemokine receptor ACKR2 suppresses Th17 responses to protein autoantigens. Immunol. Cell. Biol. 93, 167–176 (2015).

  66. 66.

    Del Prete, A., Bonecchi, R., Vecchi, A., Mantovani, A. & Sozzani, S. CCRL2, a fringe member of the atypical chemoattractant receptor family. Eur. J. Immunol. 43, 1418–1422 (2013).

  67. 67.

    Otero, K. et al. Nonredundant role of CCRL2 in lung dendritic cell trafficking. Blood 116, 2942–2949 (2010).

  68. 68.

    Del Prete, A. et al. The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage. Blood 130, 1223–1234 (2017).

  69. 69.

    Monnier, J. et al. Expression, regulation, and function of atypical chemerin receptor CCRL2 on endothelial cells. J. Immunol. 189, 956–967 (2012).

  70. 70.

    Gonzalvo-Feo, S. et al. Endothelial cell-derived chemerin promotes dendritic cell transmigration. J. Immunol. 192, 2366–2373 (2014).

  71. 71.

    Sozzani, S. et al. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J. Immunol. 155, 3292–3295 (1995).

  72. 72.

    Chen, K. et al. The formylpeptide receptor 2 (Fpr2) and its endogenous ligand cathelin-related antimicrobial peptide (CRAMP) promote dendritic cell maturation. J. Biol. Chem. 289, 17553–17563 (2014).

  73. 73.

    Dumitriu, I. E., Bianchi, M. E., Bacci, M., Manfredi, A. A. & Rovere-Querini, P. The secretion of HMGB1 is required for the migration of maturing dendritic cells. J. Leukoc. Biol. 81, 84–91 (2007).

  74. 74.

    Morelli, A., Larregina, A., Chuluyan, I., Kolkowski, E. & Fainboim, L. Expression and modulation of C5a receptor (CD88) on skin dendritic cells. Chemotactic effect of C5a on skin migratory dendritic cells. Immunology 89, 126–134 (1996).

  75. 75.

    Gutzmer, R. et al. Human plasmacytoid dendritic cells express receptors for anaphylatoxins C3a and C5a and are chemoattracted to C3a and C5a. J. Invest. Dermatol. 126, 2422–2429 (2006).

  76. 76.

    Liu, S. et al. Complement C1q chemoattracts human dendritic cells and enhances migration of mature dendritic cells to CCL19 via activation of AKT and MAPK pathways. Mol. Immunol. 46, 242–249 (2008).

  77. 77.

    Vegh, Z., Kew, R. R., Gruber, B. L. & Ghebrehiwet, B. Chemotaxis of human monocyte-derived dendritic cells to complement component C1q is mediated by the receptors gC1qR and cC1qR. Mol. Immunol. 43, 1402–1407 (2006).

  78. 78.

    Idzko, M. et al. Nucleotides induce chemotaxis and actin polymerization in immature but not mature human dendritic cells via activation of pertussis toxin-sensitive P2y receptors. Blood 100, 925–932 (2002).

  79. 79.

    Ring, S. et al. Regulatory T cell-derived adenosine induces dendritic cell migration through the Epac-Rap1 pathway. J. Immunol. 194, 3735–3744 (2015).

  80. 80.

    Li, X. et al. Plasmin triggers chemotaxis of monocyte-derived dendritic cells through an Akt2-dependent pathway and promotes a T-helper type-1 response. Arterioscler. Thromb. Vasc. Biol. 30, 582–590 (2010).

  81. 81.

    Sozzani, S. et al. Human monocyte-derived and CD34 + cell-derived dendritic cells express functional receptors for platelet activating factor. FEBS Lett. 418, 98–100 (1997).

  82. 82.

    Angeli, V. et al. Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity 21, 561–574 (2004).

  83. 83.

    Robbiani, D. F. et al. The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell 103, 757–768 (2000).

  84. 84.

    Legler, D. F., Krause, P., Scandella, E., Singer, E. & Groettrup, M. Prostaglandin E2 is generally required for human dendritic cell migration and exerts its effect via EP2 and EP4 receptors. J. Immunol. 176, 966–973 (2006).

  85. 85.

    Sawada, Y. et al. Resolvin E1 inhibits dendritic cell migration in the skin and attenuates contact hypersensitivity responses. J. Exp. Med. 212, 1921–1930 (2015).

  86. 86.

    Gatto, D. et al. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat. Immunol. 14, 446–453 (2013).

  87. 87.

    Czeloth, N. et al. Sphingosine-1 phosphate signaling regulates positioning of dendritic cells within the spleen. J. Immunol. 179, 5855–5863 (2007).

  88. 88.

    Lamana, A. et al. CD69 modulates sphingosine-1-phosphate-induced migration of skin dendritic cells. J. Invest. Dermatol. 131, 1503–1512 (2011).

  89. 89.

    Wittamer, V. et al. Specific recruitment of antigen-presenting cells by chemerin, a novel processed ligand from human inflammatory fluids. J. Exp. Med. 198, 977–985 (2003).

  90. 90.

    Vermi, W. et al. Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. J. Exp. Med. 201, 509–515 (2005).

  91. 91.

    De Palma, G. et al. The possible role of ChemR23/Chemerin axis in the recruitment of dendritic cells in lupus nephritis. Kidney Int. 79, 1228–1235 (2011).

  92. 92.

    Parolini, S. et al. The role of chemerin in the colocalization of NK and dendritic cell subsets into inflamed tissues. Blood 109, 3625–3632 (2007).

  93. 93.

    Albanesi, C. et al. Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment. J. Exp. Med. 206, 249–258 (2009).

  94. 94.

    Skrzeczynska-Moncznik, J. et al. Potential role of chemerin in recruitment of plasmacytoid dendritic cells to diseased skin. Biochem. Biophys. Res. Commun. 380, 323–327 (2009).

  95. 95.

    Seeger, P., Musso, T. & Sozzani, S. The TGF-beta superfamily in dendritic cell biology. Cytokine Growth Factor. Rev. 26, 647–657 (2015).

  96. 96.

    Gutzmer, R. et al. Human dendritic cells express the IL-18R and are chemoattracted to IL-18. J. Immunol. 171, 6363–6371 (2003).

  97. 97.

    Kaser, A. et al. Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression. Blood 103, 648–655 (2004).

  98. 98.

    Teijeira, A., Russo, E. & Halin, C. Taking the lymphatic route: dendritic cell migration to draining lymph nodes. Semin. Immunopathol. 36, 261–274 (2014).

  99. 99.

    Weinstock, M., Rosenblatt, J. & Avigan, D. Dendritic cell therapies for hematologic malignancies. Mol. Ther. Methods Clin. Dev. 5, 66–75 (2017).

  100. 100.

    Seyfizadeh, N., Muthuswamy, R., Mitchell, D. A. & Nierkens, S. Migration of dendritic cells to the lymph nodes and its enhancement to drive anti-tumor responses. Crit. Rev. Oncol. Hematol. 107, 100–110 (2016).

  101. 101.

    Fiorina, P. et al. Characterization of donor dendritic cells and enhancement of dendritic cell efflux with CC-chemokine ligand 21: a novel strategy to prolong islet allograft survival. Diabetes 56, 912–920 (2007).

  102. 102.

    Ziegler, E. et al. CCL19-IgG prevents allograft rejection by impairment of immune cell trafficking. J. Am. Soc. Nephrol. 17, 2521–2532 (2006).

  103. 103.

    Del Prete, A. et al. Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice. Embo. J. 23, 3505–3515 (2004).

  104. 104.

    See P. et al. Mapping the human DC lineage through the integration of high-dimensional techniques. Science. 356, 6342 (2017).

  105. 105.

    Rose, C. E. Jr et al. Murine lung eosinophil activation and chemokine production in allergic airway inflammation. Cell. Mol. Immunol. 7, 361–374 (2010).

  106. 106.

    Baba, T., Nakamoto, Y. & Mukaida, N. Crucial contribution of thymic Sirp alpha + conventional dendritic cells to central tolerance against blood-borne antigens in a CCR2-dependent manner. J. Immunol. 183, 3053–3063 (2009).

  107. 107.

    Le Borgne, M. et al. Dendritic cells rapidly recruited into epithelial tissues via CCR6/CCL20 are responsible for CD8 + T cell crosspriming in vivo. Immunity 24, 191–201 (2006).

  108. 108.

    Cook, D. N. et al. CCR6 mediates dendritic cell localization, lymphocyte homeostasis, and immune responses in mucosal tissue. Immunity 12, 495–503 (2000).

  109. 109.

    Leon, B. et al. Regulation of T(H)2 development by CXCR5 + dendritic cells and lymphotoxin-expressing B cells. Nat. Immunol. 13, 681–690 (2012).

  110. 110.

    Bradford B. M., Reizis B., & Mabbott N. A. Oral prion disease pathogenesis is impeded in the specific absence of CXCR5-expressing dendritic cells. J. Virol. 91, 10 (2017).

  111. 111.

    Dorner, B. G. et al. Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+T cells. Immunity 31, 823–833 (2009).

  112. 112.

    Lei, Y. et al. Aire-dependent production of XCL1 mediates medullary accumulation of thymic dendritic cells and contributes to regulatory T cell development. J. Exp. Med. 208, 383–394 (2011).

  113. 113.

    Ohta, T. et al. Crucial roles of XCR1-expressing dendritic cells and the XCR1-XCL1 chemokine axis in intestinal immune homeostasis. Sci. Rep. 6, 23505 (2016).

  114. 114.

    Swiecki, M. et al. Microbiota induces tonic CCL2 systemic levels that control pDC trafficking in steady state. Mucosal Immunol. 10, 936–945 (2017).

  115. 115.

    Sawai, C. M. et al. Transcription factor Runx2 controls the development and migration of plasmacytoid dendritic cells. J. Exp. Med. 210, 2151–2159 (2013).

  116. 116.

    Sisirak, V. et al. CCR6/CCR10-mediated plasmacytoid dendritic cell recruitment to inflamed epithelia after instruction in lymphoid tissues. Blood 118, 5130–5140 (2011).

  117. 117.

    Goubier, A. et al. Plasmacytoid dendritic cells mediate oral tolerance. Immunity 29, 464–475 (2008).

  118. 118.

    Mizuno, S. et al. CCR9 + plasmacytoid dendritic cells in the small intestine suppress development of intestinal inflammation in mice. Immunol. Lett. 146, 64–69 (2012).

  119. 119.

    Hadeiba, H. et al. Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36, 438–450 (2012).

  120. 120.

    Kohara, H. et al. Development of plasmacytoid dendritic cells in bone marrow stromal cell niches requires CXCL12-CXCR4 chemokine signaling. Blood 110, 4153–4160 (2007).

  121. 121.

    Seth, S. et al. CCR7 essentially contributes to the homing of plasmacytoid dendritic cells to lymph nodes under steady-state as well as inflammatory conditions. J. Immunol. 186, 3364–3372 (2011).

  122. 122.

    Yoneyama, H. et al. Evidence for recruitment of plasmacytoid dendritic cell precursors to inflamed lymph nodes through high endothelial venules. Int. Immunol. 16, 915–928 (2004).

  123. 123.

    Vanbervliet, B. et al. Sequential involvement of CCR2 and CCR6 ligands for immature dendritic cell recruitment: possible role at inflamed epithelial surfaces. Eur. J. Immunol. 32, 231–242 (2002).

  124. 124.

    Dieu, M. C. et al. Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites. J. Exp. Med. 188, 373–386 (1998).

  125. 125.

    Cavarelli, M., Foglieni, C., Rescigno, M. & Scarlatti, G. R5 HIV-1 envelope attracts dendritic cells to cross the human intestinal epithelium and sample luminal virions via engagement of the CCR5. EMBO Mol. Med. 5, 776–794 (2013).

  126. 126.

    Bachem, A. et al. Superior antigen cross-presentation and XCR1 expression define human CD11c + CD141 + cells as homologues of mouse CD8 + dendritic cells. J. Exp. Med. 207, 1273–1281 (2010).

  127. 127.

    Chen, S. C. et al. Expression of chemokine receptor CXCR3 by lymphocytes and plasmacytoid dendritic cells in human psoriatic lesions. Arch. Dermatol. Res. 302, 113–123 (2010).

  128. 128.

    Sato, K. et al. CC chemokine receptors, CCR-1 and CCR-3, are potentially involved in antigen-presenting cell function of human peripheral blood monocyte-derived dendritic cells. Blood 93, 34–42 (1999).

  129. 129.

    Beaulieu, S. et al. Expression of a functional eotaxin (CC chemokine ligand 11) receptor CCR3 by human dendritic cells. J. Immunol. 169, 2925–2936 (2002).

  130. 130.

    Lande, R. et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449, 564–569 (2007).

  131. 131.

    Migeotte, I. et al. Identification and characterization of an endogenous chemotactic ligand specific for FPRL2. J. Exp. Med. 201, 83–93 (2005).

  132. 132.

    Liu, C. et al. Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice. J. Clin. Invest. 118, 1165–1175 (2008).

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Acknowledgements

This work was supported by AIRC (Associazione Italiana Ricerca sul Cancro); IAP (Interuniversity Attraction Poles) 7–40 program; COST action BM1404 Mye-EUNITER; CARIPLO; and Ministero Salute.

Author information

Author notes

  1. These authors contributed equally: Laura Tiberio and Annalisa Del Prete.

Affiliations

  1. Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy

    • Laura Tiberio
    • , Annalisa Del Prete
    • , Tiziana Schioppa
    • , Francesca Sozio
    • , Daniela Bosisio
    •  & Silvano Sozzani
  2. Humanitas Clinical and Research Institute, Rozzano-Milano, Italy

    • Annalisa Del Prete
    • , Tiziana Schioppa
    • , Francesca Sozio
    •  & Silvano Sozzani

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Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Silvano Sozzani.

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DOI

https://doi.org/10.1038/s41423-018-0005-3

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