Peroxisome Proliferator-Activated Receptor γ-Regulated Cathepsin D Is Required for Lipid Antigen Presentation by Dendritic Cells

Nakken, Britt; Varga, Tamás; Szatmári, István; Széles, Lajos; Gyöngyösi, Adrienn; Illarionov, Petr A.; Dezső, Balázs; Gogolák, Péter; Rajnavölgyi, Éva; Nagy, László

doi:10.4049/jimmunol.1002421

Cited by 21 publications

(20 citation statements)

References 55 publications

(62 reference statements)

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“…In the RSG and GW9662 cotreated sample, the RALDH activity was similar to vehicle-treated control DCs. During iNKT expansion, the mRNA expression of the invariant V ␣ 24-J ␣ 18 (iNKT) TCR ␣ marker gene correlates with the cell surface expression of TCR V ␣ 24 and TCR V ␤ 11 ( 48 ). We validated the RT-qPCR measurements on iNKT cells expanded by ␣ -GalCer-loaded control or RSGtreated mo-DCs ( Fig.…”

Section: Increased Raldh Activity In Ppar ␥ -Activated Mo-dcsmentioning

confidence: 83%

“…The authors are molecules ( 23,24,48 ), which is essential for ligand presentation and recognition by the iNKTs ( 26,54,55 ).…”

Section: Discussionmentioning

confidence: 99%

“…Systematic microarray analyses also revealed that the activation of PPAR ␥ by RSG regulated the expression of genes contributing primarily to fatty acid uptake, transport, lipid storage, and attenuated lipid metabolism ( 43 ). Moreover, the PPAR ␥ -regulated lipid metabolic pathways could be associated with the altered immune response of DCs ( 23,24,48 ). PPAR ␥ enhanced the lipid antigen presentation capacity of DCs via CD1d…”

Section: Ppar ␥ -Induced Inkt Expansion Is Attenuated By Rdh10 Raldhmentioning

confidence: 99%

“…The lipid antigen-presenting capacity of PPAR ␥ -activated DCs is induced and mediated through the upregulated cell surface protein expression of CD1d protein ( 23,24,48 ). Human iNKT cells respond to ␣ -GalCer, a lipid antigen restricted exclusively to CD1d molecules.…”

Section: Ppar ␥ -Induced Inkt Expansion Is Attenuated By Rdh10 Raldhmentioning

confidence: 99%

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RDH10, RALDH2, and CRABP2 are required components of PPARγ-directed ATRA synthesis and signaling in human dendritic cells

Gyöngyösi

Szatmári²,

Pap³

et al. 2013

Journal of Lipid Research

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This article is available online at http://www.jlr.org cellular retinoic acid binding protein 2 • all-trans retinoic acid • peroxisome proliferator-activated receptor ␥ There is an increasing appreciation that metabolic processes contribute to immune cell specifi cation. One of the prime examples of such regulation is the generation and function of all-trans retinoic acid (ATRA) in several cell types of the immune system, primarily in the gut. However, it remains elusive which cell types have the capacity to produce retinoic acid, which genes are required for ATRA biosynthesis and signaling, and which factors contribute to their induction in dendritic cells (DCs).Abstract All-trans retinoic acid (ATRA) has a key role in dendritic cells (DCs) and affects T cell subtype specifi cation and gut homing. However, the identity of the permissive cell types and the required steps of conversion of vitamin A to biologically active ATRA bringing about retinoic acid receptor-regulated signaling remains elusive. Here we present that only a subset of murine and human DCs express the necessary enzymes, including RDH10, RALDH2, and transporter cellular retinoic acid binding protein (CRABP)2, to produce ATRA and effi cient signaling. These permissive cell types include CD103 + DCs, granulocyte-macrophage colonystimulating factor, and interleukin-4-treated bone marrowderived murine DCs and human monocyte-derived DCs (mo-DCs). Importantly, in addition to RDH10 and RALDH2, CRABP2 also appears to be regulated by the fatty acid-sensing nuclear receptor peroxisome proliferator-activated receptor ␥ (PPAR ␥ ) and colocalize in human gut-associated lymphoid tissue DCs. In our model of human mo-DCs, all three proteins (RDH10, RALDH2, and CRABP2) appeared to be required for ATRA production induced by activation of PPAR ␥ and therefore form a linear pathway. This now functionally validated PPAR ␥ -regulated ATRA producing and signaling axis equips the cells with the capacity to convert precursors to active retinoids in response to receptor-activating fatty acids and is potentially amenable to intervention in diseases involving or affecting mucosal immunity.

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Section: Increased Raldh Activity In Ppar ␥ -Activated Mo-dcsmentioning

confidence: 83%

“…The authors are molecules ( 23,24,48 ), which is essential for ligand presentation and recognition by the iNKTs ( 26,54,55 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Ppar ␥ -Induced Inkt Expansion Is Attenuated By Rdh10 Raldhmentioning

confidence: 99%

Section: Ppar ␥ -Induced Inkt Expansion Is Attenuated By Rdh10 Raldhmentioning

confidence: 99%

See 2 more Smart Citations

RDH10, RALDH2, and CRABP2 are required components of PPARγ-directed ATRA synthesis and signaling in human dendritic cells

Gyöngyösi

Szatmári²,

Pap³

et al. 2013

Journal of Lipid Research

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show abstract

“…These proteases are involved in digestion of Ii and maturation of pro-proteins, including pro-saposins. Lack of cathepsin S [29] and L [30] results in impaired iNKT cell development, whereas cathepsin D is upregulated by activation of the peroxisome proliferatoractivated receptor (PPAR)g, which facilitates CD1d antigen presentation [31]. Proteases might also be involved in processing of lipopeptides, which can also be presented by Review Trends in Immunology March 2012, Vol.…”

Section: Reviewmentioning

confidence: 99%