In Vivo Ablation of a Dendritic Cell Subset Expressing the Chemokine Receptor XCR1

  • Hiroaki Hemmi
  • Katsuaki Hoshino
  • Tsuneyasu KaishoEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1423)


Dendritic cells (DCs) are one of the key populations controlling immune responses. To establish a cell depletion system in vivo, human diphtheria toxin (DT) receptor (DTR) is transduced to the mice in which DTR is expressed under the control of a specific promoter. In these mice, DTR-expressing cells are inducibly depleted after DT injection. Using this system, analysis of mouse models in which DTR was expressed under the CD11c promoter has contributed to our knowledge of DC biology by depleting CD11c+ cells. Other mouse models to inducibly eliminate specific DC subsets upon DT treatment have been also generated. Here, we describe a new mouse model in which the XCR1+ DC subset is inducibly and transiently depleted in vivo.


Dendritic cells Dendritic cell subset Inducible ablation of dendritic cell subsets Diphtheria toxin Diphtheria toxin receptor 



This work was supported by the Kishimoto Foundation; Grant-in-Aid for Scientific Research from Japan Society for the Promotion of Science; Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology; and the Uehara Memorial Foundation.


  1. 1.
    Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22. doi: 10.1146/annurev-immunol-100311-102839 CrossRefPubMedGoogle Scholar
  2. 2.
    Mildner A, Jung S (2014) Development and function of dendritic cell subsets. Immunity 40:642–656. doi: 10.1016/j.immuni.2014.04.016 CrossRefPubMedGoogle Scholar
  3. 3.
    Saito M, Iwawaki T, Taya C, Yonekawa H, Noda M, Inui Y, Mekada E, Kimata Y, Tsuru A, Kohno K (2001) Diphtheria toxin receptor-mediated conditional and targeted cell ablation in transgenic mice. Nat Biotechnol 19:746–750CrossRefPubMedGoogle Scholar
  4. 4.
    Jung S, Unutmaz D, Wong P, Sano G, De los Santos K, Sparwasser T, Wu S, Vuthoori S, Ko K, Zavala F, Pamer EG, Littman DR, Lang RA (2002) In vivo depletion of CD11c + dendritic cells abrogates priming of CD8+ T cells by exogenous cell-associated antigens. Immunity 17:211–220CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Probst HC, Tschannen K, Odermatt B, Schwendener R, Zinkernagel RM, Van Den Broek M (2005) Histological analysis of CD11c-DTR/GFP mice after in vivo depletion of dendritic cells. Clin Exp Immunol 141:398–404CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Sathaliyawala T, O’Gorman WE, Greter M, Bogunovic M, Konjufca V, Hou ZE, Nolan GP, Miller MJ, Merad M, Reizis B (2010) Mammalian target of rapamycin controls dendritic cell development downstream of Flt3 ligand signaling. Immunity 33:597–606CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Hochweller K, Striegler J, Hämmerling GJ, Garbi N (2008) A novel CD11c.DTR transgenic mouse for depletion of dendritic cells reveals their requirement for homeostatic proliferation of natural killer cells. Eur J Immunol 38:2776–2783. doi: 10.1002/eji.200838659 CrossRefPubMedGoogle Scholar
  8. 8.
    Meredith MM, Liu K, Darrasse-Jeze G, Kamphorst AO, Schreiber HA, Guermonprez P, Idoyaga J, Cheong C, Yao KH, Niec RE, Nussenzweig MC (2012) Expression of the zinc finger transcription factor zDC (Zbtb46, Btbd4) defines the classical dendritic cell lineage. J Exp Med 209:1153–1165. doi: 10.1084/jem.20112675 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Yamazaki C, Sugiyama M, Ohta T, Hemmi H, Hamada E, Sasaki I, Fukuda Y, Yano T, Nobuoka M, Hirashima T, Iizuka A, Sato K, Tanaka T, Hoshino K, Kaisho T (2013) Critical roles of a dendritic cell subset expressing a chemokine receptor, XCR1. J Immunol 190:6071–6082. doi: 10.4049/jimmunol.1202798 CrossRefPubMedGoogle Scholar
  10. 10.
    Kissenpfennig A, Henri S, Dubois B, Laplace-Builhé C, Perrin P, Romani N, Tripp CH, Douillard P, Leserman L, Kaiserlian D, Saeland S, Davoust J, Malissen B (2005) Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22:643–654CrossRefPubMedGoogle Scholar
  11. 11.
    Bennett CL, van Rijn E, Jung S, Inaba K, Steinman RM, Kapsenberg ML, Clausen BE (2005) Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J Cell Biol 169:569–576CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Fukaya T, Murakami R, Takagi H, Sato K, Sato Y, Otsuka H, Ohno M, Hijikata A, Ohara O, Hikida M, Malissen B, Sato K (2012) Conditional ablation of CD205+ conventional dendritic cells impacts the regulation of T-cell immunity and homeostasis in vivo. Proc Natl Acad Sci U S A 109:11288–11293. doi: 10.1073/pnas.1202208109 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Piva L, Tetlak P, Claser C, Karjalainen K, Renia L, Ruedl C (2012) Cutting edge: Clec9A+ dendritic cells mediate the development of experimental cerebral malaria. J Immunol 189:1128–1132. doi: 10.4049/jimmunol.1201171 CrossRefPubMedGoogle Scholar
  14. 14.
    Swiecki M, Gilfillan S, Vermi W, Wang Y, Colonna M (2010) Plasmacytoid dendritic cell ablation impacts early interferon responses and antiviral NK and CD8(+) T cell accrual. Immunity 33:955–966. doi: 10.1016/j.immuni.2010.11.020 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Takagi H, Fukaya T, Eizumi K, Sato Y, Sato K, Shibazaki A, Otsuka H, Hijikata A, Watanabe T, Ohara O, Kaisho T, Malissen B, Sato K (2011) Plasmacytoid dendritic cells are crucial for the initiation of inflammation and T cell immunity in vivo. Immunity 35:958–971. doi: 10.1016/j.immuni.2011.10.014 CrossRefPubMedGoogle Scholar
  16. 16.
    Lindquist RL, Shakhar G, Dudziak D, Wardemann H, Eisenreich T, Dustin ML, Nussenzweig MC (2004) Visualizing dendritic cell networks in vivo. Nat Immunol 5:1243–1250CrossRefPubMedGoogle Scholar
  17. 17.
    Satpathy AT, KC W, Albring JC, Edelson BT, Kretzer NM, Bhattacharya D, Murphy TL, Murphy KM (2012) Zbtb46 expression distinguishes classical dendritic cells and their committed progenitors from other immune lineages. J Exp Med 209:1135–1152. doi: 10.1084/jem.20120030 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    van Blijswijk J, Schraml BU, Reis e Sousa C (2013) Advantages and limitations of mouse models to deplete dendritic cells. Eur J Immunol 43:22–26. doi: 10.1002/eji.201243022 CrossRefPubMedGoogle Scholar
  19. 19.
    Yamazaki C, Miyamoto R, Hoshino K, Fukuda Y, Sasaki I, Saito M, Ishiguchi H, Yano T, Sugiyama T, Hemmi H, Tanaka T, Hamada E, Hirashima T, Amakawa R, Fukuhara S, Nomura S, Ito T, Kaisho T (2010) Conservation of a chemokine system, XCR1 and its ligand, XCL1, between human and mice. Biochem Biophys Res Commun 397:756–761. doi: 10.1016/j.bbrc.2010.06.029 CrossRefPubMedGoogle Scholar
  20. 20.
    Dorner BG, Dorner MB, Zhou X, Opitz C, Mora A, Güttler S, Hutloff A, Mages HW, Ranke K, Schaefer M, Jack RS, Henn V, Kroczek RA (2009) Selective expression of the chemokine receptor XCR1 on cross-presenting dendritic cells determines cooperation with CD8+ T cells. Immunity 31:823–833. doi: 10.1016/j.immuni.2009.08.027 CrossRefPubMedGoogle Scholar
  21. 21.
    Inaba K, Swiggard WJ, Steinman RM, Romani N, Schuler G, Brinster C (2009) Isolation of dendritic cells. Curr Protoc Immunol Chapter 3:Unit 3.7. doi: 10.1002/0471142735.im0307s86Google Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Hiroaki Hemmi
    • 1
    • 2
    • 3
  • Katsuaki Hoshino
    • 1
    • 2
    • 4
  • Tsuneyasu Kaisho
    • 1
    • 2
    • 3
    Email author
  1. 1.Laboratory for Immune Regulation, WPI Immunology Frontier Research CenterOsaka UniversitySuitaJapan
  2. 2.Laboratory of Inflammatory Regulation, RIKEN Center for Integrative Medical SciencesYokohamaJapan
  3. 3.Department of Immunology, Institute of Advanced MedicineWakayama Medical UniversityWakayamaJapan
  4. 4.Department of Immunology, Faculty of MedicineKagawa UniversityKita-gunJapan

Personalised recommendations