Summary Increased activity of T follicular helper (Tfh) cells plays a major pathogenic role in systemic lupus erythematosus (SLE). However, the mechanisms that cause aberrant Tfh cell responses in SLE remain elusive. Here we showed the OX40 ligand (OX40L)-OX40 axis contributes to the aberrant Tfh response in SLE. OX40L was expressed by myeloid antigen-presenting cells (APCs), but not B cells, in blood and in inflamed tissues in adult and pediatric SLE patients. The frequency of circulating OX40L-expressing myeloid APCs positively correlated with disease activity and the frequency of ICOS+ blood Tfh cells in SLE. OX40 signals promoted naïve and memory CD4+ T cells to express multiple Tfh cell molecules, and were sufficient to induce them to become functional B cell helpers. Immune complexes containing RNA induced OX40L expression on myeloid APCs via TLR7 activation. Our study provides a rationale to target the OX40L-OX40 axis as a therapeutic modality for SLE.

Lipopolysaccharide (LPS) activates platelets through TLR4, aiding productive sepsis, with stimulated splicing and translation of stored heteronuclear pro-Interleukin-1β (IL-1β)RNA. Although the IL1R1 receptor for IL1 shares downstream components with the TLR4 receptor, platelets are not known to express IL1R1, nor are they known to respond to this cytokine. We show by flow cytometry and western blotting that platelets express IL1R1, and that IL-1β and IL-1α stimulate heteronuclear I-1β splicing and translation of the newly made mRNA in platelets. Platelets also respond to the IL-1β they make, which is exclusively associated with shed microparticles. Specific blockade of IL1R1 with IL1 receptor antagonist (IL1Ra) suppressed platelet stimulation by IL1, so IL-1β stimulates its own synthesis in an autocrine signaling loop. Strikingly, IL1Ra inhibition, pharmacologic or genetic suppression of pro-IL-1β processing to active cytokine by caspase-1, or blockade of de novo protein synthesis also blocked LPS-induced IL-1β mRNA production. Robust stimulation of platelets by LPS therefore also required IL-1β amplification. Activated platelets made IL-1β in vivo as IL-1β rapidly accumulated in occluded murine carotid arteries by post-transcriptional RNA splicing unique to platelets. We conclude IL-1β is a platelet agonist, that IL-1β acts through an autocrine stimulatory loop, that an IL-1β autocrine loop is required to amplify platelet activation by LPS, and that platelets immobilized in occlusive thrombi are activated over time to produce IL-1β. IL1 is a new platelet agonist that promotes its own synthesis, connecting thrombosis with immunity.

A fistula that occurs in association with a malignancy of the female reproductive tract may be caused by a primary or recurrent tumor or may be a complication of surgery or radiation therapy. Identification of the cause, complexity, and location of a fistula is essential for optimal management planning. Radiologic imaging, particularly with computed tomography and magnetic resonance techniques, is invaluable for the assessment of gynecologic fistulas and may help direct the clinician toward the most appropriate management pathway. The modality and technique selected for the initial imaging evaluation depend largely on the clinical history and manifestations. However, imaging with a combination of techniques often is required for accurate diagnosis and effective treatment planning. Radiologists should be familiar with suggestive clinical signs and symptoms as well as with the characteristic appearances of rectovaginal, vesicovaginal, ureterovaginal, enterovesical, enterocutaneous, and other pelvic fistulas at multimodality imaging.

Objective: Endometrial cancer is the most common gynaecological malignancy in developed countries. Histological grade and subtype are important prognostic factors obtained by pipelle biopsy. However, pipelle biopsy ''samples'' tissue and a high-grade component that requires more aggressive treatment may be missed. The purpose of the study was to assess the use of diffusion-weighted MRI (DW-MRI) in the assessment of tumour grade in endometrial lesions. we obtained a sensitivity, specificity, positive predictive value and negative predictive value for malignancy of 87%, 100%, 100% and 85.7%, respectively. Conclusion: Tumour mean and minimum ADC values are not useful in differentiating histological tumour grade in endometrial carcinoma. However, mean ADC measurement can provide useful information in differentiating benign from malignant endometrial lesions. This information could be clinically relevant in those patients where pre-operative endometrial sampling is not possible.