, 2009; Gautier et al., 2012; Miller et al., 2012; Rivollier et al., 2012; Plantinga et al., 2013; Segura et al., 2013). In agreement with a previous study (Verstege LB42708? et al., 2008), we found that the classical resident DCs (CD14?CX3CR1+CD1c+) and pDCs (CD14?CX3CR1?CD123+) are found in similar proportions in noninflamed and inflamed mLNs and colons, and are thus unlikely to represent a recruited cell population. In human LPMC, we showed that >90% of the HLA-DR+CD172a+ cells displayed CD14, whereas it was expressed by ~50% of these cells in the mLNs. In this regard, the HLA-DR+CD172a+CD14+ colonic cells resemble the CD14+ M�� subpopulation detected in situ in intestinal CD tissues (Grimm et al., 1995a) and the so-called intermediate CD14+CD33+CD16?CD68+CX3CR1+CD70?CD123+CD1c? M��/DCs.

However, the latter are detected throughout the gut mucosa of IBD patients (Kamada et al., 2008). The intestinal intermediate CD14+ M��/DC subset drives naive T cell differentiation into Th1 and Th17 cells in vitro (Kamada et al., 2009), and thus they might fulfill the DC criteria. Furthermore, half of the HLA-DR+CD172a+ cells identified in the mLNs and LPMC also displayed DC-SIGN, in agreement with a previous report that showed high levels of DC-SIGN expression by IHC in the mucosa of CD patients (te Velde et al., 2003). This phenotype is reminiscent of in vitro�Cgenerated Mo-DCs (Baba et al., 2008) and the Mo-DCs detected in the lymphoid organs of infected mice(Cheong et al., 2010), but contrasts with recently described CD14+DC-SIGN?CD1c+ inflammatory DCs detected in the synovial fluid of rheumatoid arthritis patients (Segura et al.

, 2013). Definitive classification of HLA-DR+CD172a+ cells into M�� versus inflammatory Mo-DCs awaits further morphological and molecular studies. In contrast to murine CD103?CD11b+ M��, which all express CD172a and CX3CR1 in LP, whether they are inflammatory or not, CD172a+ cells comprised only ~15% of the HLA-DR+ cells in inflamed gut mucosa, with about ~40% displaying CX3CR1. In mice, CD172a marks all myeloid cells, including lung and intestinal M��, as well as granulocytes and mucosal CD103?CD11b+ DCs in the skin, airway, and gut (Fortin et al., 2009; Ginhoux et al., 2009; Raymond et al., 2009). Murine CD11b+CX3CR1+ cells are considered as resident mucosal tissue M�� because these cells cannot be retraced as a homogenous population in the LNs (Schulz et al., 2009). The CD11chighCD11b+CX3CR1low DCs (also called CD11c+ M��) mediate pro-Th17 cell function, as opposed to CD11c?CD11b+CX3CR1high M�� (bona fide M��; Medina-Contreras et al., 2011). Subdivisions according to the levels of CX3CR1 expression in CX3CR1-GFP mice provide Brefeldin_A further evidence for a functional dichotomy.