Relationships between Distinct Blood Monocyte Subsets and Migrating Intestinal Lymph Dendritic Cells In Vivo under Steady-State Conditions

Abstract

The origins of dendritic cells (DCs) are poorly understood. In inflammation, DCs can arise from blood monocytes (M_Os), but their steady-state origin may differ, as shown for Langerhans cells. Two main subsets of M_Os, defined by expression of different chemokine receptors, CCR2 and CX₃CR1, have been described in mice and humans. Recent studies have identified the inflammatory function of CCR2^highCX₃CR1^low M_Os but have not defined unambiguously the origin and fate of CCR2^lowCX₃CR1^high cells. In this study, we show that rat M_Os can also be divided into CCR2^highCX₃CR1^low(CD43^low) and CCR2^lowCX₃CR1^high(CD43^high) subsets with distinct migratory properties in vivo. Using whole body perfusion to obtain M_Os, including the marginating pool, we show by adoptive transfer that CD43^low M_Os can differentiate into CD43^high M_Os in blood without cell division. By adoptive transfer of blood M_Os followed by collection of pseudoafferent lymph, we show for the first time that a small proportion of intestinal lymph DCs are derived from CCR2^lowCX₃CR1^high(CD43^high) blood M_Os in vivo under steady-state conditions. This study confirms one of the possible origins of CCR2^lowCX₃CR1^high blood M_Os and indicate that they may contribute to migratory intestinal DCs in vivo in the absence of inflammatory stimuli.