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Dr. David Sancho - Dendritic cells beyond immunity

IPBS Prestige seminar

 

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David Sancho

Immunobiology Laboratory, CNIC, Madrid, Spain

Dendritic cells beyond immunity

Dendritic cells (DCs) are innate cells well-known for its role in initiation of immunity. For this purpose, they are equipped with pattern recognition receptors that sense pathogens and lead to DC activation. However, DCs can also sense tissue damage signals that affects antigen cross-presentation and CD8+ T cell priming in the context of sterile or infectious immunity (Iborra et al., 2012; Sancho et al., 2009; Zelenay et al., 2012). Using Batf3-deficient mice that lack cDC1s and DNGR-1-deficient mice, we have shown that cross-priming of CD8+ T cells is key for induction of basal anti-tumor immunity that can be rescued by checkpoint antibody therapy (Sánchez-Paulete et al., 2016). Moreover, cDC1s and cross-priming are essential for priming precursors of resident memory CD8+ T cells that confer advantage to reinfection (Iborra et al., 2016). However, DCs can also affect other processes beyond immunity and we have recently found that DNGR-1 dampens the ability of cDC1s to attract neutrophils upon tissue damage, acting as a negative feedback loop (Del Fresno et al., 2018). We are currently exploring additional aspects of the innate response regulated by DCs and that could also affect adaptive immunity.

Selected references

  • Del Fresno et al. (2018). DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment. Science 362, 351–356
  • Iborra et al. (2012). The DC receptor DNGR-1 mediates cross-priming of CTLs during vaccinia virus infection in mice. J Clin Invest 122, 1628–1643
  • Iborra et al. (2016). Optimal generation of tissue-resident but not circulating memory T cells during viral infection requires crosspriming by DNGR-1+ dendritic cells. Immunity 45, 847–860
  • Sánchez-Paulete et al. (2016). Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires BATF3-dependent dendritic cells. Cancer Discov 6, 71–79
  • Sancho et al. (2009). Identification of a dendritic cell receptor that couples sensing of necrosis to immunity. Nature 458, 899–90
  • Zelenay et al. (2012). The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice. J Clin Invest 122, 1615–1627

 

 

Contact: Yoann Rombouts (yoann.rombouts@ipbs.fr)

Note for visitors: Please come with a valid identity card

 

 

30 Oct

11:00 - 12:00

Fernand Gallais Conference room