CX3CR1+c-kit+ Bone Marrow Cells Give Rise to CD103+ and CD103− Dendritic Cells with Distinct Functional Properties

Abstract

Dendritic cells (DC) represent a rather heterogeneous cell population with regard to morphology, phenotype, and function and, like most cells of the immune system, are subjected to a continuous renewal process. CD103+ (integrin αE) DC have been identified as a major mucosal DC subset involved in the induction of tissue-specific homing molecules on T cells, but little is known about progenitors able to replenish this DC subset. Herein we report that lineage (lin)−CX3CR1+c-kit+ (GFP+c-kit+) bone marrow cells can differentiate to either CD11c+CD103− or CD11c+CD103+ DC in vitro and in vivo. Gene expression as well as functional assays reveal distinct phenotypical and functional properties of both subsets generated in vitro. CD103− DC exhibit enhanced phagocytosis and respond to LPS stimulation by secreting proinflammatory cytokines, whereas CD103+ DC express high levels of costimulatory molecules and efficiently induce allogeneic T cell proliferation. Following adoptive transfer of GFP+c-kit+ bone marrow cells to irradiated recipients undergoing allergic lung inflammation, we identified donor-derived CD103+ DC in lung and the lung-draining bronchial lymph node. Collectively, these data indicate that GFP+c-kit+ cells contribute to the replenishment of CD103+ DC in lymphoid and nonlymphoid organs.

Selective and efficient generation of functional Batf3-dependent CD103+ dendritic cells from mouse bone marrow

“…CD103 1 DCs take up antigens less efficiently than CD103 -DCs. 38 Consistently, .50% of GM-DCs incorporate high levels of ovalbumin (OVA), compared with ,10% of FL-DCs and iCD103-DCs ( Figure 5A). …”

Thymic but not splenic CD8+ DCs can efficiently cross‐prime T cells in the absence of licensing factors

“…Recently, it has been shown that CD103 1 (integrin a E ) DCs share some of the properties of the CD8 1 DCs, including crosspresentation capability and dependence on the Batf3 (Jun dimerization protein p21SNFT) transcription factor for their development [24,25]. Although it has been described that 50-70% of splenic CD8 1 DCs coexpress CD103 [12,26], we and others [27] found much lower proportions of these cells. In both C57BL/6 and Balb/c mice, only 10-20% of splenic CD8 1 DCs showed weak expression of CD103.…”

“…6B). However, we cannot rule out the possibility that CD103 [12,26]. Accordingly, it has been recently shown in two independent studies that splenic CD8 1 DCs are heterogeneous regarding their ability to cross-present antigens [11,12].…”

Respiratory Syncytial Virus-Induced Activation and Migration of Respiratory Dendritic Cells and Subsequent Antigen Presentation in the Lung-Draining Lymph Node

“…These cells might play a role in the additional activation of LN-primed T cells and/or be important as local antigen-presenting cells that stimulate effector/memory T cells that are directly recruited to inflammatory sites (37,48,49). Furthermore, they could also play a role in the production of cytokines and chemokines that are involved in the attraction of different inflammatory cell types (13). Previous studies of RSV-infected mice reported the increase of cDC and pDC populations in the lung, similar to our observations ( Fig.…”

“…cDC can be further divided based on the expression of surface markers and anatomic location. cDC in the tissue and cDC in lymph nodes (LN) appear to be different subsets arising from different pools of progenitor cells and with specialized functions (13,17,30,33,46). In the mouse lung, two major cDC populations are derived from blood monocytes.…”