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Poly(I:C)-Treated human langerhans cells promote the differentiation of CD4+ T cells producing IFN-gamma and IL-10. 2009

Laetitia Furio, and Hermine Billard, and Jenny Valladeau, and Josette Péguet-Navarro, and Odile Berthier-Vergnes
Université de Lyon, Lyon, EA 41-69, Laboratoire de Dermatologie, Pavillon R, Hôpital E. Herriot, Lyon, France.

Epidermal Langerhans cells (LCs) are the first dendritic cells to encounter skin pathogens. However, their function has recently been challenged, especially in the initiation of T-cell responses to viral antigens. We have previously reported that fresh immature human LCs express mRNA encoding TLR3. Here we analyze the response of highly purified human LCs to poly(I:C), a synthetic mimetic of viral dsRNA recognized by TLR3. We show that LCs exposed for 2 days to poly(I:C) under serum-free conditions up-regulated co-stimulatory molecules, a process associated with increased allostimulatory capacity. Furthermore, poly(I:C) significantly enhanced LC survival and induced them to produce CXCL10, IL-6, and IL-12 p40. Bioactive IL-12 p70, IL-1beta, IL-15, IL-18, and IL-23 were never detected, even after CD40 ligation. LC incubation in the presence of bafilomycin completely reversed the effect of poly(I:C) on LC phenotypic activation and survival, indicating that endosomal TLR3 is involved in this process. Most interestingly, we report here that poly(I:C)-treated LCs favored alloreactive CD4(+) T-cell differentiation toward a Th1 profile and concomitant differentiation of IL-10-producing CD4(+) T cells that might limit, at another time, the inflammatory response and subsequent tissue damage.

UI MeSH Term Description Entries
D007371 Interferon-gamma The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES. Interferon Type II,Interferon, Immune,gamma-Interferon,Interferon, gamma,Type II Interferon,Immune Interferon,Interferon, Type II
D007801 Langerhans Cells Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS. Langerhans Cell,Dendritic Cells, Dermal,Dendritic Cells, Epidermal,Dendritic Cells, Skin,Dermal Dendritic Cells,Epidermal Dendritic Cells,Skin Dendritic Cells,Cell, Dermal Dendritic,Cell, Epidermal Dendritic,Cell, Langerhans,Cell, Skin Dendritic,Cells, Dermal Dendritic,Cells, Epidermal Dendritic,Cells, Langerhans,Cells, Skin Dendritic,Dendritic Cell, Dermal,Dendritic Cell, Epidermal,Dendritic Cell, Skin,Dermal Dendritic Cell,Epidermal Dendritic Cell,Skin Dendritic Cell
D011070 Poly I-C Interferon inducer consisting of a synthetic, mismatched double-stranded RNA. The polymer is made of one strand each of polyinosinic acid and polycytidylic acid. Poly(I-C),Poly(rI).Poly(rC),Polyinosinic-Polycytidylic Acid,Polyinosinic-Polycytidylic Acid (High MW),Polyriboinosinic-Polyribocytidylic Acid,Polyribose Inosin-Cytidil,Inosin-Cytidil, Polyribose,Poly I C,Polyinosinic Polycytidylic Acid,Polyriboinosinic Polyribocytidylic Acid,Polyribose Inosin Cytidil
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015496 CD4-Positive T-Lymphocytes A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes. T4 Cells,T4 Lymphocytes,CD4-Positive Lymphocytes,CD4 Positive T Lymphocytes,CD4-Positive Lymphocyte,CD4-Positive T-Lymphocyte,Lymphocyte, CD4-Positive,Lymphocytes, CD4-Positive,T-Lymphocyte, CD4-Positive,T-Lymphocytes, CD4-Positive,T4 Cell,T4 Lymphocyte
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016753 Interleukin-10 A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein. IL-10,CSIF-10,Cytokine Synthesis Inhibitory Factor,IL10,Interleukin 10

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