Mixed Langerhans cell and interstitial/dermal dendritic cell subsets emanating from monocytes in Th2-mediated inflammatory conditions respond differently to proinflammatory stimuli

被引:17
作者
Bechetoille, Nicolas
Andre, Valerie
Valladeau, Jenny
Perrier, Eric
Dezutter-Dambuyant, Colette
机构
[1] Univ Lyon 1, INSERM U346, Hop Edouard Herriot, F-69437 Lyon 03, France
[2] COLETICA, Lyon, France
关键词
skin; differentiation; maturation;
D O I
10.1189/jlb.0205109
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The skin harbors two dendritic cell (DC) subsets, Langerhans cells (LC) and interstitial/dermal DC (IDDC), which traffic to lymph nodes after inflammation and ultraviolet stress. To demonstrate that monocytes may act as DC precursors for skin DC in postinflammatory recolonization, we generated LC and IDDC from monocytes by using cytokines related to the T helper cell type 2 environment [granulocyte macrophage-colony stimulating factor/transforming growth factor-beta/interleukin-13/tumor necrosis factor alpha (GM-CSF/TGFP/IL-beta/TNF-alpha)]. In this study, skin DC [LC as Langerin/CD207(+) cells and IDDC as DC-specific intercellular adhesion molecule-grabbing nonintegrin (SIGN)/CD209(+) cells] displayed desynchronized programs along their differentiation, activation/maturation processes in response to stimuli characteristics of a proinflammatory context. First, we demonstrate that monocytes are able to diverge simultaneously along two distinct pathways toward Langerin(+)-LC-type DC and DC-SIGN(+)-IDDC. Second, as TGF-beta is known to antagonize the TNF-alpha-induced maturation process of DC, we showed that IDDC did not mature and acquired a low CC chemokine receptor 7 (CCR7) receptor expression even when stimulated with prolonged incubation with TNF-alpha. It is striking that the LC subset is able to express a high level of CCR7 expression and the maturation marker DC-lysosome-associated membrane protein (DC-LAMP). Third, mixed LC and IDDC subsets secrete IL-10 and IL-12 when stimulated by CD40 ligand and lipopolysaccharide (LPS) but not after prolonged incubation with TNF-alpha. In contrast, LPS was a better activator of IL-10 secretion than the CD40 ligand for GM-CSF/IL-4-generated DC and for GM-CSF/TGF-beta/IL-13-generated LC and IDDC populations. To summarize, the phenotypic/migratory maturation status of LC may be more easily enhanced by stimuli mimicking a proinflammatory situation, and IDDC are more resistant. Moreover, our culture system provided a means of studying cross-talk between two skin DC outside of their respective skin compartment.
引用
收藏
页码:45 / 58
页数:14
相关论文
共 66 条
[1]   IL-13 can substitute for IL-4 in the generation of dendritic cells for the induction of cytotoxic T lymphocytes and gene therapy [J].
Alters, SE ;
Gadea, JR ;
Holm, B ;
Lebkowski, J ;
Philip, R .
JOURNAL OF IMMUNOTHERAPY, 1999, 22 (03) :229-236
[2]   TNF-α induces the generation of Langerin/(CD207)+ immature Langerhans-type dendritic cells from both CD14-CD1a- and CD14+CD1a- precursors derived from CD34+ cord blood cells [J].
Arrighi, JF ;
Soulas, C ;
Hauser, C ;
Saeland, S ;
Chapuis, B ;
Zubler, RH ;
Kindler, V .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (07) :2053-2063
[3]   High and low doses of haptens dictate whether dermal or epidermal antigen-presenting cells promote contact hypersensitivity [J].
Bacci, S ;
Alard, P ;
Dai, RP ;
Nakamura, T ;
Streilein, JW .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (02) :442-448
[4]   Immunobiology of dendritic cells [J].
Banchereau, J ;
Briere, F ;
Caux, C ;
Davoust, J ;
Lebecque, S ;
Liu, YT ;
Pulendran, B ;
Palucka, K .
ANNUAL REVIEW OF IMMUNOLOGY, 2000, 18 :767-+
[5]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[6]  
BECHETOILLE N, 2002, EXOG DERMATOL, V1, P279
[7]   A role for TGF beta 1 in Langerhans cell biology - Further characterization of the epidermal Langerhans cell defect in TGF beta 1 null mice [J].
Borkowski, TA ;
Letterio, JJ ;
Mackall, CL ;
Saitoh, A ;
Wang, XJ ;
Roop, DR ;
Gress, RE ;
Udey, MC .
JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (03) :575-581
[8]   A role for endogenous transforming growth factor beta 1 in Langerhans cell biology: The skin of transforming growth factor beta 1 null mice is devoid of epidermal Langerhans cells [J].
Borkowski, TA ;
Letterio, JJ ;
Farr, AG ;
Udey, MC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (06) :2417-2422
[9]   OBSERVATIONS ON LANGERHANS CELLS IN LEPROSY [J].
BREATHNACH, AS ;
BIRBECK, MS ;
EVERALL, JD .
BRITISH JOURNAL OF DERMATOLOGY, 1962, 74 (07) :243-253
[10]   Respective involvement of TGF-β and IL-4 in the development of Langerhans cells and non-Langerhans dendritic cells from CD34+ progenitors [J].
Caux, C ;
Massacrier, C ;
Dubois, B ;
Valladeau, J ;
Dezutter-Dambuyant, C ;
Durand, I ;
Schmitt, D ;
Saeland, S .
JOURNAL OF LEUKOCYTE BIOLOGY, 1999, 66 (05) :781-791