scholarly journals Natural Killer Cells Modulate Overt Autoimmunity to Homeostasis in Nonobese Diabetic Mice after Anti-CD3 F(ab′)2 Antibody Treatment through Secreting Transforming Growth Factor-β

2009 ◽  
Vol 175 (3) ◽  
pp. 1086-1094 ◽  
Author(s):  
Guojiang Chen ◽  
Gencheng Han ◽  
Jianan Wang ◽  
Renxi Wang ◽  
Ruonan Xu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Diabetic Mice ◽  
Antibody Treatment ◽  
Killer Cells ◽  
Nonobese Diabetic ◽  
Nonobese Diabetic Mice

scholarly journals Transcriptomic analysis of vitamin D responses in uterine and peripheral NK cells

Reproduction ◽  
2019 ◽  
Vol 158 (2) ◽  
pp. 213-223 ◽  
Author(s):  
J A Tamblyn ◽  
L E Jeffery ◽  
R Susarla ◽  
D M Lissauer ◽  
S L Coort ◽  
...  
Keyword(s):  
Vitamin D ◽  
Natural Killer Cells ◽  
Natural Killer ◽  
Transforming Growth Factor ◽  
Active Form ◽  
Transforming Growth Factor Β ◽  
Differentially Expressed ◽  
Rna Seq ◽  
Killer Cells ◽  
Adverse Pregnancy

Vitamin D deficiency is prevalent in pregnant women and is associated with adverse pregnancy outcomes, in particular disorders of malplacentation. The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is a potent regulator of innate and adaptive immunity, but its immune effects during pregnancy remain poorly understood. During early gestation, the predominant immune cells in maternal decidua are uterine natural killer cells (uNK), but the responsivity of these cells to 1,25(OH)2D3 is unknown despite high levels of 1,25(OH)2D3 in decidua. Transcriptomic responses to 1,25(OH)2D3 were characterised in paired donor uNK and peripheral natural killer cells (pNK) following cytokine (CK) stimulation. RNA-seq analyses indicated 911 genes were differentially expressed in CK-stimulated uNK versus CK-stimulated pNK in the absence of 1,25(OH)2D3, with predominant differentially expressed pathways being associated with glycolysis and transforming growth factor β (TGFβ). RNA-seq also showed that the vitamin D receptor (VDR) and its heterodimer partner retinoid X receptor were differentially expressed in CK-stimulated uNK vs CK-stimulated pNK. Further analyses confirmed increased expression of VDR mRNA and protein, as well as VDR-RXR target in CK-stimulated uNK. RNA-seq analysis showed that in CK-stimulated pNK, 1,25(OH)2D3 induced 38 and suppressed 33 transcripts, whilst in CK-stimulated uNK 1,25(OH)2D3 induced 46 and suppressed 19 genes. However, multiple comparison analysis of transcriptomic data indicated that 1,25(OH)2D3 had no significant overall effect on gene expression in either CK-stimulated pNK or uNK. These data indicate that CK-stimulated uNK are transcriptionally distinct from pNK and, despite expressing abundant VDR, neither pNK nor uNK are sensitive targets for vitamin D.

scholarly journals Expression and Function of Transforming Growth Factor β in Melioidosis

2012 ◽  
Vol 80 (5) ◽  
pp. 1853-1857 ◽  
Author(s):  
Tassili A. F. Weehuizen ◽  
Catharina W. Wieland ◽  
Gerritje J. W. van der Windt ◽  
Jan-Willem Duitman ◽  
Louis Boon ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Organ Injury ◽  
Antibody Treatment ◽  
Content Type ◽  
Smad2 Phosphorylation ◽  
Distant Organ ◽  
Proinflammatory Role ◽  
And Function

ABSTRACTMelioidosis, caused by the Gram-negative bacteriumBurkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia and northern Australia. An important controller of the immune system is the pleiotropic cytokine transforming growth factor β (TGF-β), of which Smad2 and Smad3 are the major signal transducers. In this study, we aimed to characterize TGF-β expression and function in experimental melioidosis. TGF-β expression was determined in 33 patients with culture-proven infection withB. pseudomalleiand 30 healthy controls. We found that plasma TGF-β concentrations were strongly elevated during melioidosis. In line with this finding, TGF-β expression in C57BL/6 mice intranasally inoculated withB. pseudomalleiwas enhanced as well. To assess the role of TGF-β, we inhibited TGF-β using a selective murine TGF-β antibody. Treatment of mice with anti-TGF-β antibody resulted in decreased lung Smad2 phosphorylation. TGF-β blockade appeared to be protective: mice treated with anti-TGF-β antibody and subsequently infected withB. pseudomalleishowed diminished bacterial loads. Moreover, less distant organ injury was observed in anti-TGF-β treated mice as shown by reduced blood urea nitrogen (BUN) and aspartate transaminase (AST) values. However, anti-TGF-β treatment did not have an effect on survival. In conclusion, TGF-β is upregulated duringB. pseudomalleiinfection and plays a limited but proinflammatory role during experimental melioidosis.

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