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The Active Form of Vitamin D Transcriptionally Represses Smad7 Signaling and Activates Extracellular Signal-regulated Kinase (ERK) to Inhibit the Differentiation of a Inflammatory T Helper Cell Subset and Suppress Experimental Autoimmune Encephalomyelitis.

DIR@IMTECH: CSIR-Institute of Microbial Technology

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Title The Active Form of Vitamin D Transcriptionally Represses Smad7 Signaling and Activates Extracellular Signal-regulated Kinase (ERK) to Inhibit the Differentiation of a Inflammatory T Helper Cell Subset and Suppress Experimental Autoimmune Encephalomyelitis.
 
Creator Nanduri, Ravikanth
Mahajan, Sahil
Bhagyaraj, Ella
Sethi, Kanupriya
Kalra, Rashi
Chandra, Vemika
Gupta, Pawan
 
Subject QR Microbiology
 
Description The ability of the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), to transcriptionally modulate Smads to inhibit Th17 differentiation and experimental autoimmune encephalomyelitis (EAE) has not been adequately studied. This study reports modulation of Smad signaling by the specific binding of the VDR along with its heterodimeric partner RXR to the negative vitamin D response element on the promoter of Smad7, which leads to Smad7 gene repression. The vitamin D receptor-mediated increase in Smad3 expression partially explains the IL10 augmentation seen in Th17 cells. Furthermore, the VDR axis also modulates non-Smad signaling by activating ERK during differentiation of Th17 cells, which inhibits the Th17-specific genes il17a, il17f, il22, and il23r. In vivo EAE experiments revealed that, 1,25(OH)2D3 suppression of EAE correlates with the Smad7 expression in the spleen and lymph nodes. Furthermore, Smad7 expression also correlates well with IL17 and IFNγ expression in CNS infiltered inflammatory T cells. We also observed similar gene repression of Smad7 in in vitro differentiated Th1 cells when cultured in presence of 1,25(OH)2D3. The above canonical and non-canonical pathways in part address the ability of 1,25(OH)2D3-VDR to inhibit EAE.
 
Publisher ASBMB
 
Date 2015-05-08
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://crdd.osdd.net/open/1640/1/P%20Gupta%20J.%20Biol.%20Chem.-2015-Nanduri-jbc.M114.621839.pdf
Nanduri, Ravikanth and Mahajan, Sahil and Bhagyaraj, Ella and Sethi, Kanupriya and Kalra, Rashi and Chandra, Vemika and Gupta, Pawan (2015) The Active Form of Vitamin D Transcriptionally Represses Smad7 Signaling and Activates Extracellular Signal-regulated Kinase (ERK) to Inhibit the Differentiation of a Inflammatory T Helper Cell Subset and Suppress Experimental Autoimmune Encephalomyelitis. The Journal of biological chemistry, 290 (19). pp. 12222-36. ISSN 1083-351X
 
Relation http://www.jbc.org/content/290/19/12222.long
http://crdd.osdd.net/open/1640/