Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IL-12 is a 70-kDa heterodimeric cytokine composed of a p35 chain and p40 chain. This cytokine exerts a powerful positive regulatory influence on the development of Th1 helper T-cell immune responses and is a potent inducer of IFN-gamma production and cytotoxic T cell differentiation and function. Because epidermal Langerhans cells (LC) are important members of the dendritic APC lineage family critical for initiating cell mediated immune responses, we examined LC for their ability to produce IL-12. Epidermal cell (EC) suspensions obtained from volunteers were enriched for, or depleted of, Langerhans cells (CD1a+ EC). Enriched populations contained > 90% CD1a+ cells, whereas depleted populations contained < 1% CD1a+ cells. As assessed by reverse transcription-PCR amplification, IL-12 p40 mRNA was constitutively expressed in LC RNA extracted immediately following keratome harvest, and increased spontaneously after overnight incubation. Radioimmunoassay (RIA) of IL-12 p40 protein on supernatants revealed IL-12 release by CD1a-enriched fractions of epidermal cells. Ab specific for p40 clearly demonstrated IL-12 in epidermal LC by flow cytometry. A bioassay for the functional IL-12 heterodimer (p70) indicated that LC could produce IL-12 biologic activity, which was neutralized by anti-IL-12 Ab. These results indicate that epidermal LC, in particular cultured LC maturing into dendritic cells, express IL-12 p40 mRNA, as well as p40 and functional p70 protein, and suggest that this is one mechanism behind the high potency of dendritic APCs, such as LC, to initiate Th1 type immune responses under appropriate conditions.
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PMID:IL-12 synthesis by human Langerhans cells. 856 40

Recent reports point to a role for interleukin-12 (IL-12) in regulating T- and NK-cell function, macrophage activation and initiation of Th1-type cell responses. We sought to determine whether CD1a+ dendritic cells of the skin, as major antigen-presenting cells, are a source of IL-12 and therefore important in the initiation of Th1-type cell responses. To investigate this hypothesis, we cannulated microsurgically a skin-draining lymph vessel in the lower legs of five healthy volunteers. Altogether, ten different samples, each consisting of 1 x 10(6) lymph cells, were investigated. In four of the ten samples. CD1a+ dendritic lymph cells were isolated and purified by positive selection using mouse anti-CD1a monoclonal antibodies and sheep anti-mouse antibody-coated Dynabeads. Messenger RNA levels were estimated using a nested reverse transcriptase polymerase chain reaction (nRT-PCR) method. Total RNA was extracted from the cells, reverse transcribed to cDNA and amplified using specific primers for the target gene. Amplified products were sized by electrophoresis and visualized by ethidium bromide. Expression of IL-12 p40 and p35 mRNA was detected in all samples, both whole lymph samples and the highly enriched CD1a+ dendritic cell population. Our findings demonstrate that human skin-derived CD1a+ dendritic lymph cells produce IL-12 mRNA and may therefore be an important source of IL-12. Thus one might speculate that these CD1a+ dendritic cells, through their IL-12-producing capacity, might significantly influence the balance of Th1 versus Th2 reactions ultimately occurring.
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PMID:IL-12 gene expression in human skin-derived CD1a+ dendritic lymph cells. 893 85