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

General Characteristics of Study Participants.

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

General Characteristics of Study Participants.

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

Percentage of participants in the highest tertile of hsCRP levels according to the severity of OSA in the obese and non-obese groups.

<p>Obesity was defined by a BMI ≥25 kg/m² according to the Asian-specific BMI cut-offs from the World Health Organization Report. A) Percentage of participants in the highest tertile of hsCRP levels among 3 groups of obese participants. B) Percentage of participants in the highest tertile of hsCRP levels among 3 groups of non-obese participants.</p

Estimated odds ratio of being in the highest tertile of hsCRP levels according to the severity of OSA.

<p>Estimated odds ratio of being in the highest tertile of hsCRP levels according to the severity of OSA.</p

Multivariate linear regression analyses between AHI or SaO2 nadir and hsCRP levels after adjustment for confounding factors.

<p>Multivariate linear regression analyses between AHI or SaO2 nadir and hsCRP levels after adjustment for confounding factors.</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

Fixed effects from mixed effects models estimating the longitudinal course of post FEV1 during 10 years between SHAPTB group and normal group.

<p>Fixed effects from mixed effects models estimating the longitudinal course of post FEV1 during 10 years between SHAPTB group and normal group.</p

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

Longitudinal Lung Function Decrease in Subjects with Spontaneous Healed Pulmonary Tuberculosis

<div><p>Objective</p><p>We compared the longitudinal course of post-bronchodilator Forced Expiratory Volume in 1 second (pFEV1) over a 10-year period in subjects with spontaneous healed pulmonary tuberculosis (SHPTB) with that in normal subjects.</p><p>Methods</p><p>We prospectively investigated 339 subjects with SHPTB and 3211 normal subjects. pFEV1 values measured biannually over 10 years were analyzed using mixed effects model.</p><p>Results</p><p>At baseline, there were no differences in gender, smoking amount, and mean height, except mean age (50.0 ± 8.1 VS. 48.1 ± 7.3, <i>P</i>< 0.001) between the SHPTB and normal group. 52% of the 339 participants with SHPTB and 56% of the 3211 normal participants participated till the end of study. According to the final model, the SHPTB group showed significantly larger decrease in the average pFEV1 over the time than the normal group (P< 0.001) adjusted for gender, age, height, smoking pack years, and time effects. Especially, the interaction effect between time and group was statistically significant (P = 0.036).</p><p>Conclusion</p><p>The average lung function in terms of pFEV1 decreases faster in subjects with SHPTB than in normal individuals over time.</p></div