Friday, February 12, 2010
JOURNAL CLUB: DNA Methylation controls Foxp3 gene expression
A basic science article was discussed at immunology journal club. It discusses the role of T regs and its how they come from naive T cells and what other factors triggers them.
The vast experiments done elegantly in the study concluded the following:
1. TGF-B induces FoxP3 expression in T regs but its unstable in vitro
2. Azacytidine derivatives( demethylation agent) stabalizes foxp3 expression in induced Tregs.
3. The T reg specific demthylated region (TSDR) determines transcriptional activity
4. Azacytidine promotes stable Foxp3 expression in vitro
5. In vivo induced Tregs exhibit stable Foxp3 expression and complete TSDR demethylation
6. Foxp3 Treg generated invivo by targeting of agonist ligands to dendritic cells showed long term survival in the absence of the inducing antigen and exhibited efficient TSDR demythylation.
Besides the specifics of epigenomic imprinting in the mehylation region of the T cell region which might be critical for T cell lineage, this paper I thought highlighted something very alarming. One is that TGF-B is an important promoter of T reg cells. There are drugs out there currently under development that are inhibitory to TGF-B for anti fibrotic effects. Again, we have to think of these molecules as possible bimodal and perhaps they have different functions in different disease entities.
Second is that the dendritic cells might be important players in the long term survival of Tregs. Since there are studies that show that the patients that has increase Foxp3+ Tregs, those patients post transplant do better.
Perhaps, sustaining that positive effect should be the goal in transplantation. We can perhaps then achieve tolerance. Perhaps!!
This is interesting to me as a clinician as there might be promise ahead for tolerance.
The article source is here.
A review of the Foxp3 T regs is nicely shown in recent Nature Immunology as well
Image source: http://www.scielo.br/img/revistas/abd/v81n3/e10f1.jpg
- ► 2019 (28)
- ► 2018 (57)
- ► 2017 (52)
- ► 2016 (45)
- ► 2015 (63)
- ► 2014 (95)
- ► 2013 (133)
- ► 2012 (201)
- ► 2011 (370)
- CLINICAL CASE 5
- Luminex Technology
- IN THE NEWS ---> CLASSIFICATION FOR DIABETIC NEPH...
- Nephrectomy or No Nephrectomy?
- CONSULT ROUNDS: ORTHOSTATIC PROTEINURIA
- TOPIC DISCUSSION Risk factors for bleeding post ki...
- New drugs for Hepatitis C
- CDC HIGH RISK DONORS
- TOPIC DISCUSSION: Peritoneal Dialysis First initia...
- CLINICAL CASE 4
- Adrenal Gland Transplantation
- IN THE NEWS --->Is BMT Nephropathy really mostly ...
- Sad News
- TOPIC DISCUSSION: Tamm Horsfall Mucoprotein
- TOPIC DISCUSSION: Re-evaluating the Role of Immuno...
- JOURNAL CLUB: DNA Methylation controls Foxp3 gene ...
- In the News: The era of epigenetics
- Sirolimus and tubular toxicity
- TOPIC DISCUSSION: FIBROTIC DISEASES
- IN THE NEWS --> IgA with ANCAs
- JOURNAL CLUB: Pirfenidone Is Renoprotective in Dia...
- IN THE NEWS- CKD and Proteinuria
- CLINICAL CASE 3
- Positive Cross Match, Desensitization
- CONSULT ROUNDS: Post Bone Marrow Transplant Thromb...
- ▼ February (25)