Characterization of Human Afferent Lymph Dendritic Cells from Seroma Fluids

Abstract

Dendritic cells (DCs) migrate from peripheral tissues to secondary lymphoid organs (SLOs) through the afferent lymph. Owing to limitations in investigating human lymph, DCs flowing in afferent lymph have not been properly characterized in humans until now. In this study, DCs present in seroma, an accrual of human afferent lymph occurring after lymph node surgical dissection, were isolated and analyzed in detail. Two main DC subsets were identified in seroma that corresponded to the migratory DC subsets present in lymph nodes, that is, CD14+ and CD1a+. The latter also included CD1abright Langerhans cells. The two DC subsets appeared to share the same monocytic precursor and to be developmentally related; both of them spontaneously released high levels of TGF-β and displayed similar T cell–activating and –polarizing properties. In contrast, they differed in the expression of surface molecules, including TLRs; in their phagocytic activity; and in the expression of proteins involved in Ag processing and presentation. It is worth noting that although both subsets were detected in seroma in the postsurgical inflammatory phase, only CD1a+ DCs migrated via afferent lymph under steady-state conditions. In conclusion, the high numbers of DCs contained in seroma fluids allowed a proper characterization of human DCs migrating via afferent lymph, revealing a continuous stream of DCs from peripheral regions toward SLOs under normal conditions. Moreover, we showed that, in inflammatory conditions, distinct subsets of DCs can migrate to SLOs via afferent lymph.

CD56brightPerforinlow Noncytotoxic Human NK Cells Are Abundant in Both Healthy and Neoplastic Solid Tissues and Recirculate to Secondary Lymphoid Organs via Afferent Lymph

“…We have previously reported that seroma fluids represent an accumulation of human afferent lymph consequent to a surgical interruption of lymphatic vessels draining lymph from interstitial spaces (26). We also recently demonstrated that this fluid can accumulate without major contamination by either surgery-induced exudate or leaky blood-derived cells (27) low/neg noncytotoxic NK cells (11,(36)(37)(38). This NK cell subset expresses L-selectin (CD62L) (25), which binds with high efficiency to L-selectin physiologic ligands on LN HEV.…”

“…3C). We have recently shown that cells contained in seroma fluids are in general not contaminated by either surgery-induced exudate or blood (27). In addition, seroma NK cells did not express the activation markers HLA-DR and NKp44, therefore indicating that they should not merely represent either activated cells recruited in seroma fluid or NCR + ILC3, which express NKp44.…”

Pig Skin Includes Dendritic Cell Subsets Transcriptomically Related to Human CD1a and CD14 Dendritic Cells Presenting Different Migrating Behaviors and T Cell Activation Capacities

“…Thus, CD163 pos DDC, which expressed both FcERIa and FcRg-chains mRNA, may be the only skin DC displaying a functional FcERI receptor, in agreement with an inflammatory phenotype. Interestingly, a recent paper described that MHC-II pos /CCR7 pos /CD14 pos /FcERI pos human afferent lymph cells from seroma fluid were only present during postsurgical tissue inflammation but not in healed tissue (74). We tested the CD163 pos DDC for a potential enrichment of the human infDC (54) transcriptomic signature when compared with the four other swine cell types but did not get any significant result (data not shown), precluding the possibility to be assertive about the inflammatory nature of both porcine CD163 pos DDC and human CD14 pos DDC.…”

Cross-Talks between Natural Killer Cells and Distinct Subsets of Dendritic Cells

“…All these DC subsets can migrate through the lymph to draining lymph nodes (21). Finally, in several inflammatory conditions such as atopic dermatitis, psoriasis, rheumatoid arthritis, and tumor ascites, a different DC subtype, referred to as “inflammatory DC,” has lately been described (22).…”