Identification of Bcl-6-dependent follicular helper NKT cells that provide cognate help for B cell responses.

Lipid antigens trigger help from natural killer T cells (NKT cells) for B cells, and direct conjugation of lipid agonists to antigen profoundly augments antibody responses. Here we show that in vivo, NKT cells engaged in stable and prolonged cognate interactions with B cells and induced the formation of early germinal centers. Mouse and human NKT cells formed CXCR5(+)PD-1(hi) follicular helper NKT cells (NKT(FH) cells), and this process required expression of the transcriptional repressor Bcl-6, signaling via the coreceptor CD28 and interaction with B cells. NKT(FH) cells provided direct cognate help to antigen-specific B cells that was dependent on interleukin 21 (IL-21). Unlike T cell-dependent germinal centers, those driven by NKT(FH) cells did not generate long-lived plasma cells. Our results demonstrate the existence of a Bcl-6-dependent subset of NKT cells specialized in providing help to B cells.

Roquin-2 shares functions with its paralog Roquin-1 in the repression of mRNAs controlling T follicular helper cells and systemic inflammation.

Accumulation of T follicular helper (Tfh) cells and proinflammatory cytokines drive autoantibody-mediated diseases. The RNA-binding protein Roquin-1 (Rc3h1) represses the inducible costimulator ICOS and interferon-γ (IFN-γ) in T cells to prevent Tfh cell accumulation. Unlike Rc3h1(san) mice with a mutation in the ROQ domain of Roquin-1, mice lacking the protein, paradoxically do not display increased Tfh cells. Here we have analyzed mice with mutations that eliminate the RING domain from Roquin-1 or its paralog, Roquin-2 (Rc3h2). RING or ROQ mutations both disrupted Icos mRNA regulation by Roquin-1, but, unlike the ROQ mutant that still occupied mRNA-regulating stress granules, RING-deficient Roquin-1 failed to localize to stress granules and allowed Roquin-2 to compensate in the repression of ICOS and Tfh cells. These paralogs also targeted tumor necrosis factor (TNF) in nonlymphoid cells, ameliorating autoantibody-induced arthritis. The Roquin family emerges as a posttranscriptional brake in the adaptive and innate phases of antibody responses.

Acceptability and usability of 'One Key Question'® in Australian primary health care.

BACKGROUND: Around one-third of pregnancies in women attending antenatal care are unintended. This means a substantial number of women enter pregnancy without optimising their health prior to conception. Primary care practitioners are uniquely placed to counsel women about how to plan for pregnancy and about how to avoid unintended conception. The One Key Question® (OKQ®) tool facilitates a discussion of pregnancy intention and opens up subsequent discussions regarding preconception or contraception care. This study aimed to assess the acceptability and usability of the OKQ® tool in the Australian primary care setting. METHODS: We undertook a pilot study consisting of quantitative and qualitative componentsacross two general practice settings in Sydney, New South Wales, Australia. We documented women's responses to being asked the OKQ® as part of their consultation. We collected data on the characteristics of the participating GPs and their experience of using the OKQ® tool and conducted semi-structured interviews with all participating GPs. RESULTS: Fifty-six patients were asked the OKQ®, with the majority stating they were happy to be asked about their reproductive choices and felt it was relevant to their general health. The 10 participating GPs felt the OKQ® was easy to use and although 62.5% reported it extended the consultation time, the medium time taken was 2min. GPs felt framing the OKQ® helped introduce pregnancy intention discussions into a consultation. CONCLUSIONS: The OKQ® is acceptable to patients and easy for GPs to use. This tool facilitates a proactive and routine discussion to enhance the delivery of preconception care and contraceptive counselling.

Estradiol valerate and intake of sweetened water.

Recently, it has been shown that female rats receiving very large doses (e.g., 2 mg) of estradiol valerate (EV) take considerably more alcoholic beverage than placebo controls. The question asked, with these procedures, is whether the enhanced appetite for alcoholic beverages was specific to those beverages or was a reflection of a general increase in appetite. Female rats were provided with various sweetened beverages. In one experiment, they were provided a palatable saccharin solution (0.25% solution) and a less palatable one (2% saccharin solution). EV treatment led to more intake of the palatable saccharin solution and reduced intake of the less palatable solution. EV induces changes leading to enhanced appetite for some ingesta (including palatable saccharin solutions and alcoholic beverages), but surely not all ingesta.