CD4+ T cell responses elicited by different subsets of human skin migratory dendritic cells.

Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
The Journal of Immunology (Impact Factor: 5.52). 01/2006; 175(12):7905-15. DOI: 10.4049/jimmunol.175.12.7905
Source: PubMed

ABSTRACT Skin dendritic cells (DC) are professional APC critical for initiation and control of adaptive immunity. In the present work we have analyzed the CD4+ T cell stimulatory function of different subsets of DC that migrate spontaneously from human skin explants, including CD1a+CD14- Langerhans' cells (LC), CD1a-CD14- dermal DC (DDC), and CD1a-CD14+ LC precursors. Skin migratory DC consisted of APC at different stages of maturation-activation that produced IL-10, TGF-beta1, IL-23p19, and IL-12p40, but did not release IL-12p70 even after exposure to DC1-driving stimuli. LC and DDC migrated as mature/activated APC able to stimulate allogeneic naive CD4+ T cells and to induce memory Th1 cells in the absence of IL-12p70. The potent CD4+ T cell stimulatory function of LC and DDC correlated with their high levels of expression of MHC class II, adhesion, and costimulatory molecules. The Th1-biasing function of LC and DDC depended on their ability to produce IL-23. By contrast, CD1a-CD14+ LC precursors migrated as immature-semimature APC and were weak stimulators of allogeneic naive CD4+ T cells. However, and opposite of a potential tolerogenic role of immature DC, the T cell allostimulatory and Th1-biasing function of CD14+ LC precursors increased significantly by augmenting their cell number, prolonging the time of interaction with responding T cells, or addition of recombinant human IL-23 in MLC. The data presented in this study provide insight into the function of the complex network of skin-resident DC that migrate out of the epidermis and dermis after cutaneous immunizations, pathogen infections, or allograft transplantation.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Psoriasis is a chronic inflammatory disorder characterized by an erythematous scaly plaque of the skin occasionally accompanied by systemic complications. In the psoriatic lesions, an increased number of cytokine-producing dendritic cells and activated T cells are observed which indicate that psoriasis is a prototype of an immune-mediated dermatosis. During the last decade, emerging studies demonstrate novel roles for the dendritic cell subsets in the process of disease initiation and maintenance of psoriasis. In addition, recently discovered anti-psoriatic therapies which specifically target inflammatory cytokines produced by lesional dendritic cells bring much better clinical improvement compared to conventional treatments which implicate the crucial importance of dendritic cells in psoriasis pathogenesis. This review will summarize and discuss the dendritic cell subsets of the human skin and their pathophysiological involvement in psoriasis based on mouse- and patient-oriented studies.
    BMB reports 01/2014; · 1.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cells (DCs) are the most potent antigen sensing and presenting cells in the body and are able to both initiate and fine-tune complex immune responses on a multitude of levels. In this review, we outline recent advances in our understanding of the organization of the DC network in mice and humans, the functional specialization of the DC subsets that compose these networks, and how this has enabled us to begin to elucidate cross-species parallels. Understanding the inter-relationships between DC populations in both man and mouse will ultimately allow us to exploit our knowledge of DC biology for effective therapeutic strategies.
    Current opinion in immunology 02/2014; 26C:90-99. · 10.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cells (DCs), monocytes, and macrophages are leukocytes with critical roles in immunity and tolerance. The DC network is evolutionarily conserved; the homologs of human tissue CD141(hi)XCR1(+)CLEC9A(+) DCs and CD1c(+) DCs are murine CD103(+) DCs and CD64(-)CD11b(+) DCs. In addition, human tissues also contain CD14(+) cells, currently designated as DCs, with an as-yet unknown murine counterpart. Here we have demonstrated that human dermal CD14(+) cells are a tissue-resident population of monocyte-derived macrophages with a short half-life of <6 days. The decline and reconstitution kinetics of human blood CD14(+) monocytes and dermal CD14(+) cells in vivo supported their precursor-progeny relationship. The murine homologs of human dermal CD14(+) cells are CD11b(+)CD64(+) monocyte-derived macrophages. Human and mouse monocytes and macrophages were defined by highly conserved gene transcripts, which were distinct from DCs. The demonstration of monocyte-derived macrophages in the steady state in human tissue supports a conserved organization of human and mouse mononuclear phagocyte system.
    Immunity 09/2014; · 19.80 Impact Factor

Full-text (2 Sources)

Available from
May 23, 2014