Resistance to TGFβ suppression and improved anti-tumor responses in CD8+ T cells lacking PTPN22

Transforming growth factor β (TGFβ) is important in maintaining self-tolerance and inhibits T cell reactivity. We show that CD8⁺ T cells that lack the tyrosine phosphatase Ptpn22, a major predisposing gene for autoimmune disease, are resistant to the suppressive effects of TGFβ. Resistance to TGFβ suppression, while disadvantageous in autoimmunity, helps Ptpn22‾/‾ T cells to be intrinsically superior at clearing established tumors that secrete TGFβ. Mechanistically, loss of Ptpn22 increases the capacity of T cells to produce IL-2, which overcomes TGFβ-mediated suppression. These data suggest that a viable strategy to improve anti-tumor adoptive cell therapy may be to engineer tumor-restricted T cells with mutations identified as risk factors for autoimmunity

Interaction according to urinary sodium excretion level on the association between <i>ATP2B1</i> rs17249754 and incident hypertension: the Korean genome epidemiology study

Objective: We examined an interaction according to the estimated 24-h urinary sodium excretion on the association between ATP2B1 rs17249754 and incident hypertension. Methods: We assessed the incidence of hypertension in 1780 participants aged 45 to 75 years without cardiovascular diseases. DNA genotyping was performed using the Affymetrix Single Nucleotide Polymorphism (SNP) array 5.0. Because of previously reported associations with hypertension in various populations including Koreans, ATP2B1 rs17249754 was determined. Sodium intake was assessed by estimating the 24-h urinary sodium excretion with a Kawasaki formula from a spot urine sample. We utilized Cox proportional hazard models to test an interaction according to urinary sodium excretion on the association between ATP2B1 rs17249754 and incident hypertension. Results: The incident hypertension was increased as sodium excretion level was increased. We confirmed that the ATP2B1 rs17249754 polymorphism had significant association with hypertension. We found that the association was modified by urinary sodium excretion level (p-value = 0.006); the mutant type (AA allele, previously recognized as a protective allele) with Conclusions: In this 6-year longitudinal study, our findings suggest that excessive sodium intake estimated from urinary sodium excretion significantly modified the risk of developing hypertension associated with ATP2B1 rs17249754 genetic trait. That is, carriers with ATP2B1 rs17249754 homozygote mutant allele may be at higher risk of hypertension, when they consume excessive sodium intake.</p

Supplementary_Table – Supplemental material for Longitudinal changes in left ventricular structure and function in patients with type 2 diabetes: Normal weight versus overweight/obesity

Supplemental material, Supplementary_Table for Longitudinal changes in left ventricular structure and function in patients with type 2 diabetes: Normal weight versus overweight/obesity by Seong Hwan Kim, Ki-Chul Sung, Seung Ku Lee, Juri Park, Nan Hee Kim, Sun H Kim and Chol Shin in Diabetes & Vascular Disease Research</p

Estimated odds ratio for the risk of MetS according to the combination of high hsCRP and HCY levels at 6-year follow-up.

Estimated odds ratio for the risk of MetS according to the combination of high hsCRP and HCY levels at 6-year follow-up.</p

Flow chart of the selection procedure for participants in the present study.

Flow chart of the selection procedure for participants in the present study.</p

Estimated odds ratios for risk of MetS according to hsCRP and HCY tertiles.

The odds ratio was estimated after adjusting for age, sex, smoking and alcohol status, vitamin intake, and BMI (n = 3170). P-value for interaction = 0.45, *P P <0.01.</p

General characteristics of participants according to the presence of high HCY and hsCRP levels.

General characteristics of participants according to the presence of high HCY and hsCRP levels.</p

General Characteristics of Study Participants.

<p>General Characteristics of Study Participants.</p

General Characteristics of Study Participants.

<p>General Characteristics of Study Participants.</p

Estimated odds ratios for the risk of MetS according to the combination of high hsCRP and HCY levels at baseline.

Estimated odds ratios for the risk of MetS according to the combination of high hsCRP and HCY levels at baseline.</p