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)

Human cord blood (CB) mononuclear cells were fractionated into peanut agglutinin positive (PNA+) and PNA negative (PNA-) subsets. The PNA+ subset was enriched for T6+(CD1a)Ia+ cells, which we have previously shown to resemble the Langerhans cells (LCs) of the skin, and therefore described as circulating LCs precursors. Supernatants of PNA+ and PNA- cells, and of FACS purified populations of T6+ CB cells, cultured with and without LPS, were tested for IL-1 activity. It was found that cord blood PNA+ mononuclear cells as well as purified populations of T6+ CB cells produce significant amounts of, both extracellular and cell associated, IL-1 as compared to PNA- and T6- cells, and comparable to those produced by macrophages. LPS stimulation mainly affected T6+ cells. It can be concluded that cord blood T6+ cells, presumably LCs precursors, are capable of IL-1 production.
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PMID:IL-1 production by T6 (CD1a) positive cord blood mononuclear cells (Langerhan's cell precursors?). 247 42

In this paper we demonstrate that granulocyte-macrophage CSF (GM-CSF) specifically induces the expression of CD1 molecules, CD1a, CD1b and CD1c, upon human monocytes. CD1 molecules appeared upon monocytes on day 1 of stimulation with rGM-CSF, and expression was up-regulated until day 3. Monocytes cultured in the presence of LPS, FMLP, PMA, recombinant granulocyte-CSF, rIFN-gamma, rTNF-alpha, rIL-1 alpha, rIL-1 beta, and rIL-6 remained negative. The induction of CD1 molecules by rGM-CSF was restricted to monocytes, since no such effect was observed upon peripheral blood granulocytes, PBL, and the myeloid cell lines Monomac1, Monomac6, MV4/11, HL60, U937, THP1, KG1, and KG1A. CD1a mRNA was detectable in rGM-CSF-induced monocytes but not in those freshly isolated. SDS-PAGE and immunoblotting analyses of CD1a mAb VIT6 immunoprecipitate from lysate of rGM-CSF-activated monocytes revealed an appropriate CD1a polypeptide band of 49 kDa associated with beta 2-microglobulin. Expression of CD1 molecules on monocytes complements the distribution of these structures on accessory cells, and their specific induction by GM-CSF strengthens the suggestion that CD1 is a family of crucial structures required for interaction between accessory cells and T cells.
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PMID:CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor. 767 76

Monocytes (MO) cultured for > or =5 days with either macrophage-CSF (M-CSF) or granulocyte macrophage (GM)-CSF and IL-4 differentiated without concomitant proliferation into CD14+ macrophages (Mphi) or CD1a+ dendritic cells (DC), respectively. When adherent and nonadherent CD14high Mphi from M-CSF cultures were separated and cultured further in cytokine-free medium or with GM-CSF/IL-4, most cells from both fractions that were exposed to GM-CSF/IL-4 acquired CD1a expression and DC morphology and function. Conversely, GM-CSF/IL-4 withdrawal at day 5 and additional culture of sorted CD1a+ DC for 2 to 7 days in cytokine-free medium led to cells rapidly becoming adherent CD1a-CD14+ Mphi. Replacing GM-CSF/IL-4 with M-CSF hastened the conversion of DC to Mphi without increasing cell numbers. CD1a+CD14-CD83+ mature DC were induced by a > or =2-day exposure to MO-conditioned medium, LPS, or TNF-alpha/IL-1beta. Upon cytokine removal or culture with M-CSF, DC that had been pushed to maturation by conditioned medium or LPS remained stable or died in the new environment. TNF-alpha/IL-1beta-driven DC displayed heterogeneous CD83 expression and could thus be sorted into CD83high and CD83low/- cells; in cytokine-free medium or in M-CSF, most CD83low/- cells converted to Mphi, whereas most CD83high cells remained nonadherent CD1a+CD14- or died and thus appeared truly terminally differentiated. Hence, MO are precursors of Mphi as well as of DC, with each cell type having the capability to convert into the other until late in the differentiation/maturation process. Accordingly, the cytokine environment and the presence of differentiation and/or other stimulatory signals may be the "final decision-making factors" determining whether these cells will acquire DC or Mphi characteristics and function.
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PMID:Dendritic cells as the terminal stage of monocyte differentiation. 957 66

We studied the effects of 1alpha,25-dihydroxyvitamin D3 (1alpha, 25-(OH)2D3) on differentiation, maturation, and functions of dendritic cells (DC) differentiated from human monocytes in vitro in the presence of GM-CSF and IL-4 for 7 days. Recovery and morphology were not affected by 1alpha,25-(OH)2D3 up to 100 nM. DC differentiated in the presence of 10 nM 1alpha,25-(OH)2D3 (D3-DC) showed a marked decrease in the expression of CD1a, while CD14 remained elevated. Mannose receptor and CD32 were significantly increased, and this correlated with an enhancement of endocytic activity. Costimulatory molecules such as CD40 and CD86 were slightly decreased or nonsignificantly affected (CD80 and MHC II). However, after induction of DC maturation with LPS or incubation with CD40 ligand-transfected cells, D3-DC showed marginal increases in MHC I, MHC II, CD80, CD86, CD40, and CD83. The accessory cell function of D3-DC in classical MLR was also inhibited. Moreover, allogeneic T cells stimulated with D3-DC were poor responders in a second MLR to untreated DC from the same or an unrelated donor, thus indicating the onset of a nonspecific hyporesponsivity. In conclusion, our data suggest that 1alpha,25-(OH)2D3 may modulate the immune system, acting at the very first step of the immune response through the inhibition of DC differentiation and maturation into potent APC.
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PMID:Vitamin D3 affects differentiation, maturation, and function of human monocyte-derived dendritic cells. 1077 43

FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8 (4-pyridyl) pyrazoro [5-1-c] [1,2,4] triazin-2-yl]-2-phenylethanedion sulfate monohydrate), one of the pyridinyl imidazoles, is an immunosuppressive agent which was developed to inhibit proinflammatory cytokine production. We examined the effect of FR167653 on the differentiation and maturation phases of both human bone marrow-derived dendritic cells (BM-DC) and blood monocyte-derived DC (Mo-DC). DC induced from either BM-DC or Mo-DC progenitors in the presence of FR167653 had lower expression of CD1a, CD83 and CD86 (B7.2). FR167653 also significantly suppressed the ability of Mo-DC to produce both TNF-alpha and IL-1beta in response to LPS stimulation. Mixed lymphocyte reaction (MLR) stimulation was significantly lower in FR167653-treated Mo-DC than in control Mo-DC, although the suppressive effect of FR167653 was much less on BM-DC. These results indicate novel immunosuppressive properties of FR167653, which may be therapeutically useful in controlling chronic immune and/or inflammatory diseases through down-regulation of DC differentiation and maturation.
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PMID:Down-regulation by a new anti-inflammatory compound, FR167653, of differentiation and maturation of human monocytes and bone marrow CD34+ cells to dendritic cells. 1078 47

We describe a phenotypically and functionally novel monocyte-derived dendritic cell (DC) subset, designated mDC2, that lacks IL-12 synthesis, produces high levels of IL-10, and directs differentiation of Th0/Th2 cells. Like conventional monocyte-derived DC, designated mDC1, mDC2 expressed high levels of CD11c, CD40, CD80, CD86, and MHC class II molecules. However, in contrast to mDC1, mDC2 lacked expression of CD1a, suggesting an association between cytokine production profile and CD1a expression in DC. mDC2 could be matured into CD83+ DC cells in the presence of anti-CD40 mAbs and LPS plus IFN-gamma, but they remained CD1a- and lacked IL-12 production even upon maturation. The lack of IL-12 and CD1a expression by mDC2 did not affect their APC capacity, because mDC2 stimulated MLR to a similar degree as mDC1. However, while mDC1 strongly favored Th1 differentiation, mDC2 directed differentiation of Th0/Th2 cells when cocultured with purified human peripheral blood T cells, further indicating functional differences between mDC1 and mDC2. Interestingly, the transfection efficiency of mDC2 with plasmid DNA vectors was significantly higher than that of mDC1, and therefore mDC2 may provide improved means to manipulate Ag-specific T cell responses after transfection ex vivo. Taken together, these data indicate that peripheral blood monocytes have the capacity to differentiate into DC subsets with different cytokine production profiles, which is associated with altered capacity to direct Th cell differentiation.
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PMID:Monocyte-derived CD1a+ and CD1a- dendritic cell subsets differ in their cytokine production profiles, susceptibilities to transfection, and capacities to direct Th cell differentiation. 1103 59

We investigated the involvement of mitogen-activated protein kinases (MAPKs) in the maturation of CD83(-) dendritic cells (DC) derived from human blood monocytes. Maturating agents such as LPS and TNF-alpha induced the phosphorylation of members of the three families of MAPK (extracellular signal-regulated kinase l/2, p46/54 c-Jun N-terminal kinase, and p38 MAPK). SB203580, an inhibitor of the p38 MAPK, but not the extracellular signal-regulated kinase l/2 pathway blocker PD98059, inhibited the up-regulation of CD1a, CD40, CD80, CD86, HLA-DR, and the DC maturation marker CD83 induced by LPS and TNF-alpha. In addition, SB203580 inhibited the enhancement of the allostimulatory capacity and partially prevented the down-regulation of FITC-dextran uptake induced by LPS and TNF-alpha. Likewise, SB203580 partially prevented the up-regulation of IL-1alpha, IL-1beta, IL-lRa, and TNF-alpha mRNA upon stimulation with LPS and TNF-alpha, as well as the release of bioactive TNF-alpha induced by LPS. DC maturation induced by the contact sensitizers 2,4-dinitrofluorobenzene and NiSO(4), as seen by the up-regulation of CD80, CD86, and CD83, was also coupled to the phosphorylation of p38 MAPK, and was inhibited by SB203580. The irritants SDS and benzalkonium chloride that do not induce DC maturation did not trigger p38 MAPK phosphorylation. Together, these data indicate that phosphorylation of p38 MAPK is critical for the maturation of immature DC. These results also suggest that p38 MAPK phosphorylation in DC may become useful for the identification of potential skin contact sensitizers.
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PMID:A critical role for p38 mitogen-activated protein kinase in the maturation of human blood-derived dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact sensitizers. 1123 27

Previous studies have analyzed the lymphoid and myeloid foci within the gingival mucosa in health and chronic periodontitis (CP); however, the principal APCs responsible for the formation and organizational structure of these foci in CP have not been defined. We show that in human CP tissues, CD1a(+) immature Langerhans cells predominantly infiltrate the gingival epithelium, whereas CD83(+) mature dendritic cells (DCs) specifically infiltrate the CD4(+) lymphoid-rich lamina propria. In vivo evidence shows that exacerbation of CP results in increased levels of proinflammatory cytokines that mediate DC activation/maturation, but also of counterregulatory cytokines that may prevent a Th-polarized response. Consistently, in vitro-generated monocyte-derived DCs pulsed with Porphyromonas gingivalis strain 381 or its LPS undergo maturation, up-regulate accessory molecules, and release proinflammatory (IL-1beta, PGE(2)) and Th (IL-10, IL-12) cytokines. Interestingly, the IL-10:IL-12 ratio elicited from P. gingivalis-pulsed DCs was 3-fold higher than that from Escherichia coli-pulsed DCs. This may account for the significantly (p < 0.05) lower proliferation of autologous CD4(+) T cells and reduced release of IFN-gamma elicited by P. gingivalis-pulsed DCs. Taken together, these findings suggest a previously unreported mechanism for the pathophysiology of CP, involving the activation and in situ maturation of DCs by the oral pathogen P. gingivalis, leading to release of counterregulatory cytokines and the formation of T cell-DC foci.
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PMID:Mature dendritic cells infiltrate the T cell-rich region of oral mucosa in chronic periodontitis: in situ, in vivo, and in vitro studies. 1159

Dendritic cells (DCs) play important roles in initiation and regulation of immune responses. DCs derived from human monocytes can be classified according to presence of CD1a molecules. Although CD1a+ DCs can be prepared from monocytes in media containing GM-CSF, IL-4, and FCS, it has been reported that CD1a+ DCs could not be easily obtained from monocytes using media containing human serum or plasma. In this study, we demonstrate for the first time that heparin can reliably induce differentiation of CD1a+ DCs from monocytes with or without autologous serum or plasma. The development of CD1a+ DCs is heparin concentration dependent (0-50 U/ml). Comparing with CD1a- DCs developed without heparin, CD1a+ DCs express higher CD40 and CD80 and lower CD86. Both CD1a+ and CD1a- DCs express similar levels of HLA-DR. CD80, CD86, HLA-DR, and CD40 are proportionally up-regulated when both types of DCs are stimulated with LPS or LPS plus IFN-gamma. The effect of heparin is neutralized by heparin-binding proteins, such as protamine sulfate, platelet factor-4, and beta-thromboglobulin. Functionally, heparin-treated DCs respond to LPS or LPS plus IFN-gamma with higher IL-10 and less IL-12 production than heparin-untreated DCs. Heparin-treated DCs are more potent in priming allogeneic and autologous CD4+ T cells to proliferate and to produce both type 1 and type 2 cytokines. The results of our study show that CD1a+ DCs can be prepared from monocytes ex vivo without using xenogeneic serum and may be used for immunotherapy.
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PMID:Heparin induces differentiation of CD1a+ dendritic cells from monocytes: phenotypic and functional characterization. 1180 47

P-glycoprotein (Pgp) and vaults are associated with multidrug resistance in tumor cells, but their physiological functions are not yet clear. Pgp, the prototypical transmembrane transporter molecule, may also facilitate the migration of skin dendritic cells (DC). Vaults--ribonucleoprotein cell organelles, frequently overexpressed in Pgp-negative drug-resistant tumor cells--have also been associated with intracellular transport processes. Given the pivotal role of DC in dealing with exposure to potentially harmful substances, the present study was set out to examine the expression of Pgp and vaults during differentiation and maturation of DC. DC were obtained from different sources, including blood-derived monocytes, CD34(+) mononuclear cells, and chronic myeloid leukemia cells. Whereas flow cytometric and immunocytochemical analyses showed slightly augmented levels of Pgp, up-regulation of vault expression during DC culturing was strong, readily confirmed by Western blotting, and independent of the source of DC. In further exploring the functional significance of vault expression, it was found that supplementing DC cultures with polyclonal or mAbs against the major vault protein led to lower viabilities of LPS- or TNF-alpha-matured monocytes-DC. Moreover, expression of critical differentiation, maturation, and costimulatory molecules, including CD1a and CD83, was reduced and their capacity to induce Ag-specific T cell proliferative and IFN-gamma release responses was impaired. These data point to a role for vaults in both DC survival and functioning as APC.
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PMID:Up-regulation of drug resistance-related vaults during dendritic cell development. 1182 84


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