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

Clinical and biochemical characteristics of the women with polycystic ovary syndrome and controls included in this study.

<p>Data are presented as means ± standard deviations. HDL, high-density lipoprotein; mFG, modified Ferriman-Gallwey.</p><p>Clinical and biochemical characteristics of the women with polycystic ovary syndrome and controls included in this study.</p

Clinical characteristic of subjects.

<p>Data are presented as mean ± standard deviation.</p><p>BMI, body mass index.</p

Personality Traits and Body Mass Index in a Korean Population

<div><p>Background</p><p>Overweight and obesity is a serious problem worldwide related to cardiovascular and other diseases. Personality traits are associated with the abnormal body mass indices (BMIs) indicative of overweight and obesity. However, the links between personality traits and BMI have been little studied in Korea.</p><p>Methods</p><p>We evaluated the association between personality traits and BMI in men and women using the rural Ansung and urban Ansan cohort from the Korean Genome Epidemiology Study, and the Kangbuk Samsung Hospital Cohort Study datasets. A shorter version of the original Revised Neuroticism-Extroversion-Openness Personality Inventory (NEO-PI-R) was used to measure the five-factor model of personality (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness).</p><p>Results</p><p>Data from a total of 1,495 men (mean age 60.0±9.8 years; mean BMI 24.3±3.0 kg/m²) and 2,547 women (mean age 47.0±15.5 years; mean BMI 22.8±3.4 kg/m²) were included in the analysis. Compared with the normal weight groups, overweight and obese men scored higher on openness to experience and lower on conscientiousness. Overweight and obese women scored lower on neuroticism and openness to experience and higher on agreeableness. Extraversion was positively associated with BMI in men (β = 0.032, <i>P</i><0.05). BMI and waist circumference were significantly increased in individuals who were less dutiful. In women, neuroticism was inversely associated with BMI (β = −0.026, <i>P</i><0.05). Openness to experience was negatively, and agreeableness was positively, associated with BMI (openness to experience: β = −0.072, agreeableness β = 0.068) and waist circumference (openness to experience: β = −0.202, agreeableness: β = 0.227) (<i>P</i><0.05).</p><p>Conclusion</p><p>Personality traits were associated with underweight, overweight, and obesity in men and women. Increased understanding of the underlying factors contributing to this association will aid in the prevention and treatment of abnormal BMI.</p></div

Regression analyses of personality traits, body mass index (BMI) and waist circumference, men and women.

<p>*<i>P</i><0.05 after controlling for age, age squared and education.</p

Association between Blood Lipid Levels and Personality Traits in Young Korean Women

<div><p>Abnormal lipid levels are important etiological factors associated with the development of atherosclerosis and with increased cardiovascular morbidity and mortality. Lipid levels are also influenced by lifestyle and behavioral factors, which suggests that personality traits might be related to abnormal lipid profiles. Studies on personality traits and lipid levels are relatively scarce in Korea. Therefore, the objective of this study was to examine the association between lipid levels and personality traits in young Korean women. A total of 1,701 young Korean women [mean age  = 24.9±4.6 years (range 17–39)] who volunteered for personality trait evaluation were recruited for this study. Lipid levels, including total cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride, were measured in all subjects after an overnight fast, and a low density lipoprotein (LDL) cholesterol level was calculated. The study population was divided into abnormal and normal lipid level groups according to the clinical criteria. Personality traits were measured using the Revised NEO Personality Inventory for the Five-Factor Model of personality. High neuroticism was associated with low HDL cholesterol levels. Low extraversion and openness were associated with high levels of triglyceride. At the facet level, the association between personality and lipid levels were generally consistent. Angry hostility, self-consciousness, vulnerability to stress, activity, and straightforwardness were associated with HDL cholesterol levels. Activity, positive emotion, aesthetics, actions, and deliberation were associated with triglyceride. When applying clinical criteria, conscientiousness was less likely to have abnormal total cholesterol levels. Our results showed that the women with the low HDL cholesterol levels are like to be more neurotic and the hyperglycemic women are prone to lower extraversion and openness in Korea. Understanding the associations between blood lipid levels and personality traits may have a beneficial effect for the managing of dyslipidemia.</p></div

Descriptive statistics results for study population demographics, blood lipid levels, and personality variables.

<p>Note. N = 1701.</p><p>SD: Standard deviations.</p><p>Descriptive statistics results for study population demographics, blood lipid levels, and personality variables.</p

Results for the logistic regression analyses examining the associations between blood lipid level categories and personality traits.

<p>Note. OR, odds ratio: CI, confidence interval.</p><p>Logistic regression analyses were performed after adjusted for age, BMI, systolic blood pressure, current smoking status, and drinking status.</p>a<p>Normal N = 1386, Abnormal N = 315.</p>b<p>Normal N = 1410, Abnormal N = 291.</p>c<p>Normal N = 1384, Abnormal N = 317.</p>d<p>Normal N = 1614, Abnormal N = 87.</p><p>*P<0.05. Significant results are bolded.</p><p>Results for the logistic regression analyses examining the associations between blood lipid level categories and personality traits.</p

Results of the associations between personality traits and blood lipid levels.

<p>Note. N = 1701.</p>a<p>Standardized regression coefficients adjusted with age, BMI, systolic blood pressure, current smoking status, and drinking status.</p><p>*P<0.05, **P<0.01. Significant results are bolded.</p><p>Results of the associations between personality traits and blood lipid levels.</p