Distinct Transcriptional Programs Activated by Interleukin-10 with or without Lipopolysaccharide in Dendritic Cells: Induction of the B Cell-Activating Chemokine, CXC Chemokine Ligand 13.

Perrier, Patrick; Martinez, Fernando; Locati, Massimo; Bianchi, Giuseppe; Nebuloni, Manuela; Vago, Gianluca; Bazzoni, Flavia; Sozzani, Silvano; Allavena, Paola; Mantovani, Alberto

doi:10.4049/jimmunol.173.3.2199-c

Cited by 29 publications

(40 citation statements)

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“…In agreement with the human data (Perrier et al 18 and references therein; Huang et al 19 ), treatment with LPS had a profound effect on the transcriptional profile of the mouse DC. Additionally, the set of mouse genes modulated by LPS corresponds to those reported for human.…”

Section: Transcriptional Profile Of Lps-treated DCsupporting

confidence: 88%

TGFβ-dependent gene expression profile during maturation of dendritic cells

et al. 2007

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Primary immune response to pathogens involves the maturation of antigen-presenting dendritic cells (DC). Bacterial lipopolysacharride (LPS) is a potent inducer of DC maturation, whereas the transforming growth factor b (TGFb) attenuates much of this process. Here, we analyzed the global gene expression pattern in LPS-treated bone marrow derived DC during inhibition of their maturation process by TGFb. Exposure of DC to LPS induces a pronounced cell response, manifested in altered expression of a large number of genes. Interestingly, TGFb did not affect most of the LPS responding genes. Nevertheless, analysis identified a subset of genes that did respond to TGFb, among them the two inflammatory cytokines interleukin (IL)-12 and IL-18. Expression of IL-12, the major proinflammatory cytokine secreted by mature DC, was downregulated by TGFb, whereas the expression level of the proinflammatory cytokine IL-18, known to potentiate the IL-12 effect, was upregulated. Expression of the peroxisome proliferator-activated receptor g (PPARg) increased in response to TGFb, concomitantly with reduced expression of chemokine receptor 7 (CCR7). This finding supports the possibility that TGFbdependent inhibition of CCR7 expression in DC is mediated by PPARg.

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Section: Transcriptional Profile Of Lps-treated DCsupporting

confidence: 88%

TGFβ-dependent gene expression profile during maturation of dendritic cells

et al. 2007

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“…This phenomenon, which we previously reported in a published abstract [27], was recently confirmed independently by Carlsen et al [19]. They also extended this observation by demonstrating, in agreement with the work of Perrier et al [28], that CXCL13 can be produced by non-stromal hemopoietic cells of the monocyte lineage. Having established that CXCL13 can be produced in the absence of an advanced organizational stage and a critical cell mass (Grade 3), we next examined the relationship between CXCL13 production and lymphoid tissue formation as it progresses through enlargement phases analyzed according to the grading score.…”

Section: Cxcl13 In Situ Production and Microstructural Lymphoid Organsupporting

confidence: 87%

Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis

Paoletti²,

et al. 2005

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CXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ-like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non-organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T-B compartmentalization, CD21 + follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.

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“…Thus, regardless of the actual identity of this band, it seems unlikely that the mechanisms underlying the action of IL-10 in neutrophils involve a modulation of Bcl-3. Another potential intermediate for the modulation of gene expression by IL-10 is SOCS-3, an intracellular protein that is rapidly induced by IL-10 in many cell types [26][27][28] and whose overexpression has been shown to inhibit numerous pro-inflammatory actions of LPS in murine macrophage J774 cells [26] as well as the phosphorylation of STAT3 tyrosine residues activated by IL-10 [26,29]. Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In other words, the up-regulation of IL-10R1 (and the subsequent formation of a fully competent IL-10R) does not suffice per se to allow IL-10 to readily modulate the expression of LPS-induced cytokine mRNA, as observed in "time 0" PBMC. We have then investigated the role of potential newly synthesized candidates recently proposed to take part in the antiinflammatory activities of IL-10 or in the mechanisms of suppression of TNF-a production, including SOCS-3, HO-1, and Bcl-3 [22,[25][26][27][28]. According to our experiments, the induction of antigenic SOCS-3, HO-1, and Bcl-3 in neutrophils appeared, again, not sufficient for IL-10 to exert a modulatory action on gene expression at early times after LPS stimulation.…”

Section: Requirement Of De Novo Protein Synthesis For the Inhibitory mentioning

confidence: 99%