, 2011). The latter may develop into the former at steady state (Bain et al., 2013). However, the human CD172a+CX3CR1+ cells described in this study appear distinct from the resident CD11c?CD11b?CD14?HLA-DR+CD13+ M�� selleck chemical MEK162 that represent the largest population of mononuclear phagocytes in the human body (Smythies et al., 2005; Smith et al., 2011). The killing and elimination of invading pathogens are the primary functions of human intestinal M��. As such, the intestinal M�� are essentially protective (Smith et al., 2011). Because the ubiquitously expressed CD47 Ag delivers a ��do not eat me�� signal to CD172a+ APC, the lack of CD172a expression on resident human intestinal M�� may facilitate their phagocytic function (van den Berg and van der Schoot, 2008).

The challenge with human studies is to define which of the circulating monocyte or DC populations may represent the precursors of the HLA-DR+CD172a+ cells detected in the lymphoid and nonlymphoid tissues. The inflammatory CD14bright monocytes, which are the human counterparts of murine Ly6Chigh cells, may represent candidate precursors of the proinflammatory CD14+ cells in the gut or Mo-DCs in the mLNs (Tamoutounour et al., 2012). Of interest, autologous CD14+ monocytes injected into CD patients are retraced as intestinal CD14+ cells, and the transfer of Ly6Chigh cells into mice generates CD103?CX3CR1+ mononuclear phagocytes (Grimm et al., 1995b; Varol et al., 2009). Here, we showed that the proportion of circulating HLA-DR+CD172abrightCD14brightCD16? monocytes is similar in PBL from control and CD donors.

However, HLA-DR+CD172a+CD14+ cells accumulated in the inflamed colons, in agreement with the detection of CD14brightCD103? cells in the ileum of CD donors (Bain et al., 2013). We further postulate that intestinal HLA-DR+CD172a+ cells that may coexpress E-Cadherin and/or CX3CR1 have the capacity to migrate into mLNs because they were also found in increased proportions in the mLNs of CD patients. Recent studies indicate that CD103?CX3CR1+CD172a+ mononuclear phagocytes, previously considered as a nonmigratory intestinal cell population, traffic from gut to mLNs in mice (Cerovic et al., 2013; Diehl et al., 2013). However, the HLA-DR+CD172a+CD1c?CX3CR1+cells, which coexpress CD14 and E-Cadherin, may originate from circulating CD14+ monocytes that are recruited directly to mLNs from the bloodstream (Siddiqui et al.

, 2010; Tamoutounour et al., 2012). Human CD14+ M�� produce IL12p40, TNF, IL-6, and IL-1�� in response to in vitro culture with commensal bacteria (Kamada et al., 2008). Our data demonstrated Dacomitinib that, among the ex vivo�Cisolated HLA-DR+ cells, only those that coexpressed CD172a and were recognized by CD47-Var1 produced IL-1�� in the absence of external stimuli in the gut mucosa and mLNs. The inflammasome is a crucial molecular platform that regulates the activation of caspase-1 and the processing of IL-1��.