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

Gene ontology biological process annotations associated with target genes of differentially expressed miRNAs in women with polycystic ovary syndrome.

<p>Gene ontology biological process annotations associated with target genes of differentially expressed miRNAs in women with polycystic ovary syndrome.</p

A boxplot for the relative expression of serum miRNAs in women with PCOS and control subjects from the quantitative real-time polymerase chain reaction analysis.

<p>(a-c) For each miRNA, the line inside the box is the median. The top and bottom lines of the box are the first and third quartiles, respectively. The top and bottom whiskers are the 5^th and 95^th percentiles, respectively. Any data beyond these whiskers were shown as cycles. miRNA, microRNA; PCOS, polycystic ovary syndrome; Ct, the threshold cycle.</p

Relative expression of serum miRNAs between women with PCOS and control subjects (2^-ΔCt).

Relative expression of serum miRNAs between women with PCOS and control subjects (2-ΔCt).</p

Multiple linear regression analysis of relative expression of miRNA-6767-5p with reproductive and metabolic variables.

<p>Multiple linear regression analysis of relative expression of miRNA-6767-5p with reproductive and metabolic variables.</p

Clinical and biochemical characteristics of women with PCOS and control subjects.

<p>Clinical and biochemical characteristics of women with PCOS and control subjects.</p

Correlation analysis between the relative expression of miRNA-6767-5p and reproductive/metabolic variables in total subjects.

<p>Correlation analysis between the relative expression of miRNA-6767-5p and reproductive/metabolic variables in total subjects.</p

Cardiovascular outcomes of study participants.

Data are presented as frequencies and proportions. CVD, cardiovascular disease. (DOCX)</p

Cardiovascular disease incidence according to waist circumference categories.

HRs were adjusted for age, smoking status, alcohol consumption status, level of physical activity, total cholesterol, hypertension, and diabetes mellitus status. WC, waist circumference; CVD, cardiovascular disease; HR, hazard ratio.</p

Demographic and clinical characteristics of the subjects according to waist circumference categories.

Demographic and clinical characteristics of the subjects according to waist circumference categories.</p