Specific B-cell subsets can regulate T-cell immune responses, and are termed regulatory B cells (Breg). The majority of Breg cells described in mouse and man have been identified by IL-10 production and are known to suppress allergy and autoimmunity. However, Breg cell mediated immune suppression, independent of IL-10, also occurs. Here we show that Breg cells play a critical role in regulating humoral immunity mediated by CD4 þ CXCR5 þ PD-1 þ follicular helper T cells, and can suppress inflammation in autoimmune disease through elevated expression of PD-L1. We have also identified that these B cells are resistant to aCD20 B-cell depletion. This work describes how Breg cells are critical in humoral homoeostasis and may have implications for the regulation of autoimmune diseases.

Ion-sensitive responsive polymers are prepared under fully aqueous conditions using controlled radical polymerization. Variations in comonomer content and sequence lead to temperature and salt-dependent solution behavior, with cloud-points ranging by +/-40 degrees C following addition of Hofmeister series salts. A "hybrid" block copolymer, composed of a statistical sequence of monomers tipped with a hydrophilic block, formed stable micelle-like assemblies that exhibited burst release of an encapsulated model drug in response to addition of a kosmotrope, Na2SO4, at room temperature.

ILC2s interact with CD4 T cells during immune responses against parasitic helminths. Schwartz et al. describe that PD-L1–expressing pulmonary ILC2s stimulate CD4 T cells via PD-1 to up-regulate the type 2 master transcription factor GATA3 and thereby promote IL-13 production from Th2 cells.

BackgroundNeuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive of neuroblastoma patient survival and has been reported as a tumor suppressor in a variety of other cancers. WEE1, a tyrosine kinase regulator of the cell cycle and predicted target of miR-497, has emerged as an oncogene in several cancer types and therefore represents an attractive potential target for novel therapy approaches in high-risk neuroblastoma. Our aim was to investigate the potential tumor suppressive role of miR-497 in high-risk neuroblastoma.MethodsExpression levels of miR-497 and WEE1 in tissues and cells were determined using RT-PCR. The effect of miR-497 and siWEE1 on cell viability was evaluated using MTS assays, apoptosis levels were determined using FACS analysis of Annexin V/PI stained cells, and target protein expression was determined using western blot. Luciferase reporter plasmids were constructed to confirm direct targeting. Results were reported as mean±S.E.M and differences were tested for significance using 2-tailed Students t-test.ResultsWe determined that miR-497 expression was significantly lower in high-risk MYCN amplified (MNA) tumors and that low miR-497 expression was associated with worse EFS and OS in our cohort. Over-expression of miR-497 reduced cell viability and increased apoptosis in MNA cells. We identified WEE1 as a novel target for miR-497 in neuroblastoma. Furthermore, our analysis showed that high WEE1 levels are significantly associated with poor EFS and OS in neuroblastoma and that siRNA knockdown of WEE1 in MNA cell lines results in significant levels of apoptosis, supporting an oncogenic role of WEE1 in neuroblastoma. Cisplatin (CDDP) treatment of both miR-497 over-expressing cells and WEE1 inhibited cells, resulted in a significant increase in apoptosis in MNA cells, describing a synergistic effect and therefore a potential therapeutic for high-risk neuroblastoma.ConclusionOur study’s results are consistent with miR-497 being a candidate tumor suppressor in neuroblastoma, through the direct targeting of WEE1. These findings re-enforce the proposal of WEE1 as a therapeutic target in neuroblastoma.

The use of live helminth infections is currently in clinical trials as a novel approach for the treatment of a range of allergic and autoimmune diseases. This rapid progression from observational studies some 20 years ago to helminth clinical trials can be attributed to huge advances in not just pre-clinical and clinical evidence, pertaining to the efficacy of these parasites in unrelated diseases, but also a greater understanding of the complex immunological mechanisms that underpin these effects. Helminths have exerted significant evolutionary selective pressures on the host immune genome or "immunome". Studies on helminths were pivotal in a paradigm shift in immunology with recent discoveries of a number of novel immune cell populations. Critically, these new discoveries highlight the need to further understand the underlying mechanism behind the desirable therapeutic effects that helminths offer. With these unknown unknowns there is the distinct possibility that a true, fundamental modus operandi for helminth therapy will arrive long after it has been established in the clinic.