Non-classical monocytes are reported to arise by conversion of classical monocytes in the mouse

Non-classical monocytes are reported to arise by conversion of classical monocytes in the mouse. CD303 and CD304. Although not related directly to plasma cells they retain subtle lymphoid features and unique secretory properties. Homologues are recognized in many species. CD14+ DCs found in tissues and lymph nodes are a third subset of CD11c+ myeloid cells originally described as interstitial DCs. They are more monocyte-like or macrophage-like than CD1c+ and CD141+ mDCs and may arise from classical monocytes. Equivalent ARHGAP26 cells have recently been found in mice as a new monocyte-derived subset of CD11b classical DCs that expresses or ESAM. Langerhans cells (LCs) and microglia are two specialized self-renewing DC populations found in stratified squamous epithelium and parenchyma of the brain, respectively. The LCs are capable of differentiating into migratory DCs whereas microglia are considered as a type of macrophage by many authors. Recent reviews provide excellent summaries of microglia and they will not be discussed further.17 FunctionalCanatomical classification of dendritic cells A functionalCanatomical classification derived from murine studies recognizes that DC function is intimately linked to location.18 Primarily this separates migratory DCs that have trafficked through the tissues, from resident DCs that arise in lymph nodes directly from the blood. Two further compartments also merit consideration: blood DCs and inflammatory DCs. The distribution of human DC subsets is summarized in Fig.?2. Open in a separate window Figure 2 The distribution of major human dendritic cell (DC) subsets in blood, epithelial tissues and lymph nodes. Broken arrows indicate relationships that require further confirmation in humans. Human DCs can be generated either from granulocyteCmacrophage progenitors (GMP) or multi-lymphoid progenitors (MLP) both of which ultimately arise from haematopoietic stem cells (HSC). Classical monocytes, blood myeloid DC (mDC) and plasmacytoid DC (pDC) are putative precursors of tissue and lymphoid DCs. Non-classical monocytes are reported to arise by conversion of classical monocytes in Dehydroepiandrosterone the mouse. Inflammatory DCs and CD14+ DCs have transcriptional profiles suggesting that they arise from monocytes; likewise tissue CD1c+ DCs and CD141+ DCs are related to their blood counterparts. Myeloid DCs and Langerhans cells (LCs) both form interdigitating cells in skin-draining lymph nodes. CD14+ DCs and pDCS are also found in nodes but may arise directly from the blood rather than by migration from tissues. Blood/precursor DCs Blood DCs are well defined in humans, and are likely to be precursors of tissue and lymphoid organ DCs. In support of this, blood contains pDCs, CD1c+ and CD141+ mDCs in immature forms of those found in tissues and lymph nodes.19C20 Mice also have blood pDCs and circulating precursors of classical DCs known as pre-cDCs. Pre-cDCs are blood mDCs in all but name and comprise multiple subsets that may correspond to the two human myeloid blood DCs.21 Non-lymphoid/tissue/migratory DCs Most epithelial tissues contain non-lymphoid or migratory DCs whose function is to acquire antigen and migrate via the afferent lymphatics to lymph nodes. Quiescent interstitial tissues contain CD1c+ mDCs, CD141+ mDCs and CD14+ DCs but few pDCs.8C22 Epidermal LCs also migrate to form a component of afferent lymphatic DCs23 but it remains uncertain whether CD14+ DCs are migratory.24 Lymphoid/resident DCs Lymphoid tissue also contains a large cohort of blood-derived non-migratory lymphoid or resident DCs. In the steady state, these may be difficult to separate from migratory DCs derived from the tissues. Human lymphoid tissue is less well described than mouse but contains CD1c+ mDCs, CD141+ mDCs and pDC in the steady state, in addition to a number of CD14+ populations.8C22 The contingent of resident lymphoid and migratory DCs in lymph nodes increases markedly during inflammation. Inflammatory DCs The content of tissues and lymphoid organs is dramatically altered during inflammation principally by the recruitment Dehydroepiandrosterone of granulocytes, classical monocytes and pDCs. Steady-state DC populations become more difficult to detect either because they migrate or are diluted by recruited cells. CD14+ classical Dehydroepiandrosterone monocytes are the putative precursors of inflammatory DCs. It is not known whether blood DCs are also recruited during inflammation but expression of CD62L and CXCR3, (receptor for interferon–inducible chemokines CXCL9,10,11) suggests that they are competent to extravasate. Recent work confirms that inflammatory exudates contain two populations with polarized DC and macrophage properties. 9 The relative contributions of migrating tissue DCs and newly recruited inflammatory DCs to the initiation of immunity, is a critical unresolved problem in humans. Dehydroepiandrosterone CD1c+ myeloid DCs CD1c+ mDCs are the major population of human mDCs in Dehydroepiandrosterone blood, tissues and lymphoid organs. They were originally recognized in the blood as a fraction of HLA-DR+ lineage? cells expressing myeloid antigens CD11b, CD11c, CD13, CD33, CD172 (SIRPa) and CD45RO25.