The role of CD1d in intestinal tumor development — ASN Events
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  3. The role of CD1d in intestinal tumor development

The role of CD1d in intestinal tumor development (#134)

Chiara Ceriotti 1 , Melanie Jaeger 1 , Emilie Huc-Claustre 2 , Sebastian Zeissig 1 3
  1. DFG Center for Regenerative Therapies Dresden, Dresden, Germany
  2. CRCT Cancer Research Center of Toulouse, Toulouse, France
  3. Universitätsklinikum Carl Gustav Carus, Dresden, Germany

CD1d-dependent natural killer T (NKT) cell regulate tumor development and both the promotion of intestinal tumor growth as well as its inhibition by NKT cells has been described (1–7). While these divergent effects at least partially originate from cell-specific roles of type I and type II NKT cell subsets (8–10), it is not known whether antigen presenting cells (APCs) also contribute in a cell-specific manner to NKT cell-dependent regulation of intestinal tumor development. We have recently demonstrated opposing roles of intestinal epithelial cells (IECs) and myeloid cells in CD1d- and NKT cell-mediated regulation of intestinal inflammation (11). We therefore investigated in the present study whether similar cell type-specific effects of CD1d exist in the control of intestinal tumor development.

The Cre/loxP system was used to generate conditional cell-specific CD1d knockout (KO) mice that lack CD1d in IECs or myeloid cells in models of spontaneous, orthotopic intestinal tumor development (Apc Min/+ and Apc flox mice). Neither mice with individual deletion of CD1d in myeloid cells nor those with IEC-specific CD1d deletion showed significant difference in tumor growth and multiplicity compared to CD1d-sufficient littermates. Constitutive Cd1d1-/- mice showed a mild reduction in tumor size compared to Cd1d1+/- littermates, while tumor multiplicity was unaltered.

Together, these data show that in the specific microbial and nutritional context provided in our facility, individual deletion of CD1d in IECs or myeloid cells has little impact on intestinal tumor development, while constitutive deletion of CD1d is associated with reduced tumor growth. Differences in the extent of CD1d- and NKT cell-dependent promotion of tumor growth between similar mouse strains maintained in different facilities (10) further suggests that CD1d-mediated control of tumor development is dependent on environmental factors such as the microbiota and/or nutrition.

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