Interleukin 9 (IL-9)-producing helper T (Th9) cells have a crucial function in allergic inflammation, autoimmunity, immunity to extracellular pathogens and anti-tumor immune responses. In addition to Th9, Th2, Th17 and Foxp3+ regulatory T (Treg) cells produce IL-9. A transcription factor that is critical for IL-9 induction in Th2, Th9 and Th17 cells has not been identified. Here we show that the forkhead family transcription factor Foxo1 is required for IL-9 induction in Th9 and Th17 cells. We further show that inhibition of AKT enhances IL-9 induction in Th9 cells while it reciprocally regulates IL-9 and IL-17 in Th17 cells via Foxo1. Mechanistically, Foxo1 binds and transactivates IL-9 and IRF4 promoters in Th9, Th17 and iTreg cells. Furthermore, loss of Foxo1 attenuates IL-9 in mouse and human Th9 and Th17 cells, and ameliorates allergic inflammation in asthma. Our findings thus identify that Foxo1 is essential for IL-9 induction in Th9 and Th17 cells.

The identification of neuroprotectin D1 (NPD1), a biosynthetic product of docosahexaenoic acid (DHA), in brain and retina as well as the characterization of its bioactivity, is generating a renewed interest in the functional role and pathophysiological significance of omega-3 fatty acids in the central nervous system.Neurotrophins, particularly pigment epithelium-derived factor (PEDF), induce NPD1 synthesis and its polarized apical secretion, implying paracrine and autocrine bioactivity of this lipid mediator. Also, DHA and PEDF synergistically activate NPD1 synthesis and antiapoptotic protein expression and decreased proapoptotic Bcl-2 protein expression and caspase 3 activation during oxidative stress.In experimental stroke, endogenous NPD1 synthesis was found to be upregulated, and the infusion of the lipid mediator into the brain under these conditions revealed neuroprotective bioactivity of NPD1.The hippocampal CA1 region from Alzheimer's disease (AD) patients (rapidly sampled) shows a major reduction in NPD1.The interplay of DHA-derived neuroprotective signaling aims to counteract proinflammatory, celldamaging events triggered by multiple, converging cytokine and amyloid peptide factors, as in the case of AD. Generation of NPD1 from DHA thereby appears to redirect cellular fate toward successful preservation of retinal pigment epithelial (RPE)-photoreceptor cell integrity and brain cell aging. The Bcl-2 pro-and antiapoptotic proteins, neurotrophins, and NPD1, lie along a cell fateregulatory pathway whose component members are highly interactive, and have potential to function cooperatively in cell survival. Agents that stimulate NPD1 biosynthesis, NPD1 analogs, or dietary regimens may be useful as new preventive/therapeutic strategies for neurodegenerative diseases.

The cytokine interleukin-1β (IL-1β) is a key mediator of anti-microbial immunity as well as autoimmune inflammation. Production of IL-1β requires transcription by innate immune receptor signaling and maturational cleavage by inflammasomes. Whether this mechanism applies to IL-1β production seen in T cell-driven autoimmune diseases remains unclear. Here, we describe an inflammasome-independent pathway of IL-1β production that was triggered upon cognate interactions between effector CD4 + T cells and mononuclear phagocytes (MPs). The cytokine TNF produced by activated CD4 + T cells engaged its receptor TNFR on MPs, leading to pro-IL-1β synthesis. Membrane-bound FasL, expressed by CD4 + T cells, activated death receptor Fas signaling in MPs resulting in caspase-8-dependent pro-IL-1β cleavage. The T cell-instructed IL-1β Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Genital tuberculosis is an important cause of infertility in developing countries and hysterosalpingography (HSG) is the initial procedure performed for the evaluation. Reviewing 37 cases of female genital tuberculosis, we encountered various appearances on HSG. Of 579 HSGs performed over a period of 4 years, 492 (85%) were performed as part of infertility work up. Genital tuberculosis was found in 6.3% of all the patients who underwent HSGs and 7.5% of all patients investigated for infertility. The various features of proven tuberculosis cases are illustrated in this pictorial review. We briefly discuss the pathology and these appearances along with radiopathological correlation.

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Recurrent spontaneous haemarthrosis are commonly seen in patients affected by haemophilia. The knee and the elbow are most commonly affected and both are amenable to arthroscopic treatment. Arthroscopic synovectomy is indicated after failure of appropriate medical management with recurrent bleeding. Many patients also demonstrate motion loss and functional deterioration. The benefits of arthroscopic synovectomy include the ability to perform adequate synovial debridement, but also concomitant lysis of adhesion and capsular release to regain range of motion. Results of arthroscopic synovectomy demonstrate a significant decrease in episodes of haemarthrosis, and significant improvement in pain, range of motion and function. The primary predictor of outcome is degree of pre-existing degenerative changes within the joint. In more severe cases, the results of arthroscopic synovectomy are unpredictable and serious consideration should be given to primary arthroplasty.

Summary Activation of B and T lymphocytes leads to major remodelling of the metabolic landscape of the cells enabling their post‐activation functions. However, naive B and T lymphocytes also show metabolic differences, and the genesis, nature and functional significance of these differences are not yet well understood. Here we show that resting B‐cells appeared to have lower energy demands than resting T‐cells as they consumed lower levels of glucose and fatty acids and produced less ATP. Resting B‐cells are more dependent on OXPHOS, while T‐cells show more dependence on aerobic glycolysis. However, despite an apparently higher energy demand, T lineage cells showed lower rates of protein synthesis than equivalent B lineage stages. These metabolic differences between the two lineages were established early during lineage differentiation, and were functionally significant. Higher levels of protein synthesis in B‐cells were associated with increased synthesis of MHC class II molecules and other proteins associated with antigen internalization, transport and presentation. The combination of higher energy demand and lower protein synthesis in T‐cells was consistent with their higher ATP‐dependent motility. Our data provide an integrated perspective of the metabolic differences and their functional implications between the B and T lymphocyte lineages.

Following Japanese encephalitis virus (JEV) infection neutralizing antibodies are shown to provide protection in a significant proportion of cases, but not all, suggesting additional components of immune system might also contribute to elicit protective immune response. Here we have characterized the role of T cells in offering protection in adult mice infected with JEV. Mice lacking α/β–T cells (TCRβ–null) are highly susceptible and die over 10–18 day period as compared to the wild-type (WT) mice which are resistant. This is associated with high viral load, higher mRNA levels of proinflammatory cytokines and breach in the blood-brain-barrier (BBB). Infected WT mice do not show a breach in BBB; however, in contrast to TCRβ-null, they show the presence of T cells in the brain. Using adoptive transfer of cells with specific genetic deficiencies we see that neither the presence of CD4 T cells nor cytokines such as IL-4, IL-10 or interferon-gamma have any significant role in offering protection from primary infection. In contrast, we show that CD8 T cell deficiency is more critical as absence of CD8 T cells alone increases mortality in mice infected with JEV. Further, transfer of T cells from beige mice with defects in granular lytic function into TCRβ-null mice shows poor protection implicating granule-mediated target cell lysis as an essential component for survival. In addition, for the first time we report that γ/δ-T cells also make significant contribution to confer protection from JEV infection. Our data show that effector CD8 T cells play a protective role during primary infection possibly by preventing the breach in BBB and neuronal damage.