Trends in Immunology
ReviewInflammatory dendritic cells in mice and humans
Section snippets
Overview of DC subsets
DCs are a heterogeneous population comprising several subsets that can be separated based on phenotypic markers. Murine steady-state DC subsets can be classified into two main categories: plasmacytoid DCs (pDCs) and classical DCs (cDCs). cDCs derive from a common precommitted precursor, the pre-cDC, that is dependent on Fms-like tyrosine kinase 3-ligand (Flt3L) [1], and they share key functional properties, such as constitutive expression of MHC class II molecules, ability to process antigens
Definition of infDCs
In mice, infDCs were initially identified as MHC II+ CD11b+ CD11c+ F4/80+ Ly6C+ DCs that are absent from steady-state tissues and lymphoid organs, and differentiate from monocytes during inflammation [8]. InfDCs have since been described during pathogenic inflammation (cutaneous Leishmania major infection 8, 9, systemic Listeria monocytogenes infection 10, 11, 12, systemic Trypanosoma brucei infection 13, 14, fungal infections 15, 16, 17, genital herpes simplex virus (HSV)-2 infection [18],
Development of infDCs
InfDCs were initially described to differentiate in situ from monocytes recruited to the sites of inflammation [8]. Several lines of evidence support a precursor–product relation between monocytes and infDCs. In vivo transfer experiments have shown that injected monocytes differentiate into infDCs in different inflammation models 8, 12, 13, 15, 23, 24, 29, 30, 31, 39. A similar conclusion was drawn using a reporter mouse expressing fluorescent CCR2 (a chemokine receptor expressed by monocytes
infDCs and T cell activation
Several studies demonstrated that infDCs can present antigens to CD4+ T cells. InfDCs purified from lymphoid organs 8, 15, 19, 26, 27, 28, 29 or tissues [18] can activate antigen-specific CD4+ T cells ex vivo. Indirect evidence also suggests that infDCs can activate CD4+ T cells in vivo in peripheral tissues [44]. In addition, CD4+ T cell activation in vivo is abrogated during A. fumigatus infection in mice depleted of CCR2+ cells [15] and strongly decreased in CCR2-deficient but not in
Human infDCs
In humans, several DC subsets have also been identified, including lymphoid-organ-resident and migratory DCs. infDCs have been described in several pathological inflammatory situations: atopic dermatitis, psoriasis, rheumatoid arthritis, and tumor ascites. Inflammatory dendritic epidermal cells (IDECs) were first described in the skin of atopic dermatitis patients [45]. These cells express surface markers different from Langerhans cells and dermal DCs from healthy skin. Recently, we identified
Concluding remarks
InfDCs are a distinct subset of DCs that appear during inflammation and derive from monocytes that differentiate in situ at the site of inflammation. InfDCs can migrate to the draining lymph nodes and activate CD4+ and CD8+ T cells. InfDCs have also been shown to stimulate effector or memory T cells directly in the inflamed tissue. Human equivalents of infDCs have been identified in several inflammatory diseases and in tumor ascites.
Although recent work provides insight into the development and
Acknowledgments
Our work is supported by INSERM, European Research Council (2008-AdG n°233062 PhagoDC) and Ligue contre le Cancer. The authors have no competing financial interests.
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