Peroxisome Proliferator-Activated Receptor γ Control of Dendritic Cell Function Contributes to Development of CD4+ T Cell Anergy

Klotz, Luisa; Dani, Indra; Edenhofer, Frank; Nolden, Lars; Evert, Bernd O.; Paul, Bianca; Kolanus, Waldemar; Klockgether, Thomas; Knolle, Percy A.; Diehl, Linda

doi:10.4049/jimmunol.178.4.2122

Cited by 109 publications

(123 citation statements)

References 43 publications

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“…Besides their involvement in the macrophage for antiinflammatory response, activated PPARs play an important role in the production of retinoic acid, which regulates dendritic cell function and maturation, and the induction of CD4 + T-cell anergy (Klotz et al, 2007;Szatmari et al, 2006;. While proinflammatory cytokines inhibit PPARγ activity, interleukin (IL)-4 stimulates PPARγ interaction with STAT6 to promote gene expression in macrophages and dendritic cells (Szanto et al, 2010).…”

Section: Ppars and Inflammationmentioning

confidence: 99%

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Choi¹,

Bothwell

2012

Molecules and Cells

149

111

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Members of the nuclear receptor superfamily function as transcription factors involved in innate and adaptive immunity as well as lipid metabolism. These highly conserved proteins participate in ligand-dependent or -independent regulatory mechanisms that affect gene expression. Peroxisome proliferator-activated receptors (PPARs), which include PPARα, PPARβ/δ, and PPARγ, are a group of nuclear receptor proteins that play diverse roles in cellular differentiation, development, and metabolism. Each PPAR subfamily is activated by different endogenous and synthetic ligands. Recent studies using specific ligand treatments and cell type-specific PPAR knockout mice have revealed important roles for these proteins in T-cell-related autoimmune diseases. Moreover, PPARs have been shown to regulate T-cell survival, activation, and CD4 + T helper cell differentiation into the Th1, Th2, Th17, and Treg lineages. Here, we review the studies that provide insight into the important regulatory roles of PPARs in T-cell activation, survival, proliferation, differentiation, and autoimmune disease.

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Section: Ppars and Inflammationmentioning

confidence: 99%

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Choi¹,

Bothwell

2012

Molecules and Cells

149

111

View full text Add to dashboard Cite

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“…Furthermore, PPAR-c via induction of retinoic acid synthesis induces CD1d expression in DCs resulting in NKT cell proliferation and possibly altered lipid presentation by CD1 molecules [164,165]. Absence of PPAR-c in DCs increases their immunogenicity [166]. LXR also alters DC phenotype by decreasing IL-12, increasing IL-10 secretion and blocking its T-cell stimulatory ability [167].…”

Section: Involvement Of Adaptive Immune Response In Atherogenesismentioning

confidence: 99%

Nuclear receptors in macrophages: A link between metabolism and inflammation

Szántó

Röszer

2007

FEBS Letters

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Subclinical inflammation is a candidate etiological factor in the pathogenesis of metabolic syndrome and in the progression of atherosclerosis. A central role for activated macrophages has been elucidated recently as important regulators of the inflammatory process in atherosclerosis. Macrophage differentiation and function can be modulated by a class of transcription factors termed nuclear receptors. These are activated by intermediary products of basic metabolic processes. In this review the contribution of peroxisome proliferator-activated receptors and liver X receptors to macrophage functions in inflammation and lipid metabolism will be discussed in light of their roles in macrophages during atherosclerosis.In the past decade much effort has been made to understand the mechanisms how lipids are handled by macrophages and how inflammation could promote the atherogenic process. Here, we also provide an overview of these two fields.

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“…Previously, we and others have shown that activation of PPAR␥ suppresses DC maturation (22,23). Sustained activation of PPAR␥ in DCs prevented LPS-induced up-regulation of costimulatory molecules and production of proinflammatory cytokines.…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

“…Sustained activation of PPAR␥ in DCs prevented LPS-induced up-regulation of costimulatory molecules and production of proinflammatory cytokines. In consequence, decreased signaling via signals 2 and 3 resulted in severely impaired priming of CD4 ϩ T cells by PPAR␥-activated DCs both in vitro and in vivo (23).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

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Increased Antigen Cross-Presentation but Impaired Cross-Priming after Activation of Peroxisome Proliferator-Activated Receptor γ Is Mediated by Up-Regulation of B7H1

Klotz

Hucke

Thimm

et al. 2009

The Journal of Immunology

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Dendritic cells are able to take up exogenous Ags and present Ag-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of APCs, has been demonstrated to target soluble Ags exclusively toward cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model Ag OVA. We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in dendritic cells induced up-regulation of the coinhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in the development of therapeutic approaches aimed at the control of excessive immune responses, e.g., in T cell-mediated autoimmunity.

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Peroxisome Proliferator-Activated Receptor γ Control of Dendritic Cell Function Contributes to Development of CD4+ T Cell Anergy

Cited by 109 publications

References 43 publications

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

The Nuclear Receptor PPARs as Important Regulators of T-Cell Functions and Autoimmune Diseases

Nuclear receptors in macrophages: A link between metabolism and inflammation

Increased Antigen Cross-Presentation but Impaired Cross-Priming after Activation of Peroxisome Proliferator-Activated Receptor γ Is Mediated by Up-Regulation of B7H1

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