The origin and development of nonlymphoid tissue CD103+ DCs

By Michel C. Nussenzweig, Florent Ginhoux, Kang Liu, J. Helft, M. Bogunovic, M. Greter, D. Hashimoto, J. Price, Na Yin, Jonathan S. Bromberg and 3 more. Journal of Experimental Medicine, 2009

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CD103+ dendritic cells (DCs) in nonlymphoid tissues are specialized in the cross-presentation of cell-associated antigens. However, little is known about the mechanisms that regulate the development of these cells. We show that two populations of CD11c+MHCII+ cells separated on the basis of CD103 and CD11b expression coexist in most nonlymphoid tissues with the exception of the lamina propria. CD103+ DCs are related to lymphoid organ CD8+ DCs in that they are derived exclusively from pre-DCs under the control of fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), and IFN regulatory protein 8 (IRF8). In contrast, lamina propria CD103+ DCs express CD11b and develop independently of Id2 and IRF8. The other population of CD11c+MHCII+ cells in tissues, which is CD103−CD11b+, is heterogenous and depends on both Flt3 and MCSF-R. Our results reveal that nonlymphoid tissue CD103+ DCs and lymphoid organ CD8+ DCs derive from the same precursor and follow a related differentiation program.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/dae87540cdae906e201cfb35256c89b52571d0d1

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Citations in the corpus

Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells (2010, background): “However, Batf3-dependent CD11b– CD103+ Langerin+ DCs related to CD8+ DCs have recently been identified in mouse peripheral tissues (Bedoui et al., 2009; Ginhoux et al., 2009; Edelson et al., 2010; Henri et al., 2010).”
The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting. (2013, background): “Thus, the pre-cDC is a cDC-restricted progenitor that constantly leaves the BM for the periphery to differentiate locally into cDCs (16, 31, 33) (Figure 3).”
Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas (2010, background): “Pre-cDCs move into the blood to seed both lymphoid and nonlymphoid tissues forming CD11chi, MHC IIhi DCs (Liu et al., 2009; Ginhoux et al., 2009).”
Type I interferon is selectively required by dendritic cells for immune rejection of tumors (2011, positive): “…were originally identified as the CD8  + DCs that resided in lymphoid organs; yet subsequent work showed that they are closely related to another small DC subset residing in peripheral tissues that lack CD8  but express CD103 (Hildner et al., 2008; Ginhoux et al., 2009; Edelson et al., 2010).”
IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses (2013, methodology): “NLT CD11b+ DCs can be derived from both bone marrow (BM) DC specific progenitors and monocytes in steady state (Ginhoux et al., 2009) and are partially dependent on both FLT3 and the colony-stimulating factor 1 receptor (CSF-1R) (Ginhoux et al., 2009).”
Monocyte recruitment during infection and inflammation (2011, background): “However, it has also been suggested that CD103 + DCs in the lung can be derived from CDP”
Human Tissues Contain CD141hi Cross-Presenting Dendritic Cells with Functional Homology to Mouse CD103+ Nonlymphoid Dendritic Cells (2012, background): “The lectins DEC205 and langerin are also expressed on DCs of this lineage in a number of different sites (Contreras et al., 2010; Ginhoux et al., 2009).”
Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells (2010, background): “During the review of our manuscript, a separate report also identified the developmental relationship between peripheral CD103+ DCs and lymphoid organ–resident CD8+ cDCs (Ginhoux et al., 2009).”
Tissue resident macrophages self-maintain locally throughout adult life with minimal contribution from circulating monocytes (2013, methodology): “Parabiosis Parabiotic mice were generated as reported (Ginhoux et al., 2009) from ageand weight-matched CD45.”