IgG regulates the CD1 expression profile and lipid antigen-presenting function in human dendritic cells via FcγRIIa

Smed‐Sörensen, Anna; Moll, Markus; Cheng, Tan Yun; Loré, Karin; Norlin, Anna-Carin; Perbeck, L.; Moody, D. Branch; Spetz, Anna-Lena; Sandberg, Johan K.

doi:10.1182/blood-2007-07-099549

Cited by 47 publications

(47 citation statements)

References 44 publications

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“…2 MoDC differentiation (14,15). Such variability between MoDCs originated from different blood donors in our laboratory, and MoDCs generated in different laboratories suggested the possibility that differences in the experimental procedure might have a strong influence on MoDC development.…”

Section: Cd209mentioning

confidence: 99%

Dendritic Cell Reprogramming by Endogenously Produced Lactic Acid

Nasi

Fekete

Krishnamurthy

et al. 2013

The Journal of Immunology

153

118

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The demand for controlling T cell responses via dendritic cell (DC) vaccines initiated a quest for reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce inflammatory or suppressor programs during differentiation, and we identified a powerful autocrine pathway that, in a cell concentration–dependent manner, strongly interferes with inflammatory DC differentiation. MoDCs developing at low cell culture density have superior ability to produce inflammatory cytokines, to induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no inflammatory cytokines upon activation. DCs from high-density cultures maintained more differentiation plasticity and can develop to osteoclasts. The cell concentration–dependent pathway was independent of peroxisome proliferator–activated receptor γ (PPARγ), a known endogenous regulator of MoDC differentiation. Instead, it acted through lactic acid, which accumulated in dense cultures and induced an early and long-lasting reprogramming of MoDC differentiation. Our results suggest that the lactic acid–mediated inhibitory pathway could be efficiently manipulated in developing MoDCs to influence the immunogenicity of DC vaccines.

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Section: Cd209mentioning

confidence: 99%

Dendritic Cell Reprogramming by Endogenously Produced Lactic Acid

Nasi

Fekete

Krishnamurthy

et al. 2013

The Journal of Immunology

153

118

View full text Add to dashboard Cite

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“…Monocytes were negatively selected from buffy coats using the RosetteSep Monocyte Enrichment Kit (1 mL/10 mL buffy coat; StemCell Technologies) and differentiated into DCs, as shown previously, 33,34 at a density of 5 ϫ 10 5 cells/mL in RPMI 1640 completed with 10% FCS, 1mM sodium pyruvate, 10mM HEPES, 2mM L-glutamine, and 1% streptomycin and penicillin (all from Invitrogen Life Technologies), with GM-CSF (250 ng/ mL; PeproTech) and IL-4 (6.5 ng/mL; R&D Systems) for 6 or 7 days. The cells were phenotyped with Abs against CD14, CD1a (both from DakoCytomation), CD3, and CD19 (both from BD Biosciences).…”

Section: Differentiationmentioning

confidence: 99%

Single-stranded DNA oligonucleotides inhibit TLR3-mediated responses in human monocyte-derived dendritic cells and in vivo in cynomolgus macaques

Sköld

Hašan

Vargas

et al. 2012

Blood

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TLR3 is a key receptor for recognition of double-stranded RNA and initiation of immune responses against viral infections. However, hyperactive responses can have adverse effects, such as virusinduced asthma. Strategies to prevent TLR3-mediated pathology are therefore desired. We investigated the effect of single-stranded DNA oligonucleotides (ssDNA-ODNs) on TLR3 activation. Human monocyte-derived dendritic cells up-regulate maturation markers and secrete proinflammatory cytokines on treatment with the synthetic TLR3 ligand polyinosine-polycytidylic acid (poly I:C). These events were inhibited in cultures with ssDNA-ODNs. Poly I:C activation of nonhematopoietic cells was also inhibited by ssDNA-ODNs. The uptake of poly I:C into cells was reduced in the presence of ssDNA-ODNs, preventing TLR3 engagement from occurring. To confirm this inhibition in vivo, we administered ssDNAODNs and poly I:C, alone or in combination, via the intranasal route in cynomolgus macaques. Proinflammatory cytokines were detected in nasal secretions in the poly I:C group, while the levels were reduced in the groups receiving ssDNA-ODNs or both substances. IntroductionThe immune system distinguishes between self and non-self with a variety of pattern recognition receptors such as Toll-like receptors (TLRs), C-type lectins, RIG-I-like receptors, and Nod-like receptors. [1][2][3][4] Ten genes for TLRs exist in humans and they are expressed on the cellular surface or in the intracellular endosomal compartment. 2 For activation to take place, the receptors form homodimers or heterodimers and transmit a signal via the adaptor proteins MyD88 and/or TIR domain-containing adapter-inducing INF-␤ (TIRF). The extracellular TLRs recognize conserved glycoprotein and lipopeptide structures specific to microbial organisms, while the endosomal receptors recognize nucleic acids. 2 TLR3 is the only receptor transmitting its signal merely via the adaptor protein TRIF and it does so in response to double-stranded RNA (dsRNA) present in, for example, viral genomes or their intermediates during the replication cycle. 5,6 However, selfproduced dsRNA can also engage TLR3 when released from damaged tissues. 7-9 The synthetic ligand polyinosine-polycytidylic acid (poly I:C) is commonly used to target TLR3 in vaccine adjuvant constructs and in different experimental conditions. 4,7,10 Immune activation mediated via TLR3 has been shown to be important in clearance of viral infections because of a robust induction of IL-12 and type I interferons. 5 Furthermore, studies revealing its ability to mediate efficient cross-presentation of endocytosed Ags 11,12 have made TLR3 an interesting target in vaccine adjuvant development. 4,13,14 However, several reports have also implicated TLR3 in having detrimental effects during certain infections or conditions. 5,6 Cells infected with Epstein-Barr virus have been shown to secrete virally encoded RNA detected by TLR3 that results in systemic pathologic immune activation. 15 The role of TLR3 in viral CNS infections is debated, w...

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“…We have reported previously that IgG regulates the expression of CD1 molecules on human DCs in vitro, via an CD32a (FcgRIIa)-dependent mechanism. 6 In the present study, we took advantage of the low IgG levels in treatment-naïve patients with common variable immunodeficiency (CVID) to investigate if IgG might regulate the CD1 expression profile also in vivo. 7,8 Peripheral blood mononuclear cells isolated from 13 patients newly diagnosed with CVID according to the criteria established by the Pan-American Group for Immunodeficiency before the onset of intravenous immunoglobulin (IVIg) replacement therapy were analyzed by flow cytometry.…”

mentioning

confidence: 99%