PU.1 and BCL11B sequentially cooperate with RUNX1 to anchor mSWI/SNF to poise the T cell effector landscape.

Adaptive immunity relies on specialized effector functions elicited by lymphocytes, yet how antigen recognition activates appropriate effector responses through nonspecific signaling intermediates is unclear. Here we examined the role of chromatin priming in specifying the functional outputs of effector T cells and found that most of the cis-regulatory landscape active in effector T cells was poised early in development before the expression of the T cell antigen receptor. We identified two principal mechanisms underpinning this poised landscape: the recruitment of the nucleosome remodeler mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) by the transcription factors RUNX1 and PU.1 to establish chromatin accessibility at T effector loci; and a 'relay' whereby the transcription factor BCL11B succeeded PU.1 to maintain occupancy of the chromatin remodeling complex mSWI/SNF together with RUNX1, after PU.1 silencing during lineage commitment. These mechanisms define modes by which T cells acquire the potential to elicit specialized effector functions early in their ontogeny and underscore the importance of integrating extrinsic cues to the developmentally specified intrinsic program.

AIRE in context: Leveraging chromatin plasticity to trigger ectopic gene expression.

The emergence of antigen receptor diversity in clonotypic lymphocytes drove the evolution of a novel gene, Aire, that enabled the adaptive immune system to discriminate foreign invaders from self-constituents. AIRE functions in the epithelial cells of the thymus to express genes highly restricted to alternative cell lineages. This somatic plasticity facilitates the selection of a balanced repertoire of T cells that protects the host from harmful self-reactive clones, yet maintains a wide range of affinities for virtually any foreign antigen. Here, we review the latest understanding of AIRE's molecular actions with a focus on its interplay with chromatin. We argue that AIRE is a multi-valent chromatin effector that acts late in the transcription cycle to modulate the activity of previously poised non-coding regulatory elements of tissue-specific genes. We postulate a role for chromatin instability-caused in part by ATP-dependent chromatin remodeling-that variably sets the scope of the accessible landscape on which AIRE can act. We highlight AIRE's intrinsic repressive function and its relevance in providing feedback control. We synthesize these recent advances into a putative model for the mechanistic modes by which AIRE triggers ectopic transcription for immune repertoire selection.

Vitellogenin expression in the oilseed rape pest Meligethes aeneus.

When investigating insecticide resistance of pest insects, for example, the pollen beetle Meligethes aeneus, it is relevant to differentiate toxicological and molecular genetic data between male and female specimens. A molecular sex determination method would allow resistance testing to be run without prior sorting of the samples. A one-step quantitative RT-PCR method for quantification of the yolk protein vitellogenin expression in the pollen beetle was established. The expression level of vitellogenin relative to tubulin was determined. Pollen beetles were tested at different time points during their development to determine if vitellogenin is a reliable molecular marker for detection of sexually mature females. The differentiation between females and males by relative expression of vitellogenin to tubulin is conditional regarding the life cycle. Sexually mature females and males could easily be distinguished, whereas immature specimens could not be seperated. Vitellogenin expression is a successful marker for identification of sexually mature pollen beetles. Females from the spring populations showed vitellogenin expression when the temperature was above 10.2°C. Further, detailed observations of vitellogenin throughout the spring indicated a strong relationship between daily temperatures and vitellogenin expression, which is an indicator of oviposition ability.

Graft-versus-host disease (GvHD) of the tongue and of the oral cavity: a large retrospective study.

Graft-versus-host disease (GvHD) causes severe mucositis, impairs feeding and favors infection. The objective of this study was to identify the impact of GvHD in the oral cavity. We reviewed all consecutive patients who developed oral GvHD after HSCT. The study period was over 14 years. 53 patients were identified. M/F = 1.4; median age was 48.6 years; the median follow-up was for up to 3 years and 6 months. Conditioning regimens included several drugs (e.g., busulfan, cyclophosphamide and fludarabine). In 11 cases, radiotherapy (RT) was also used. Patients treated with RT were more likely to have tooth decay requiring fillings (p = 0.029), to need canal root interventions (p = 0.005) and to have tartar requiring oral hygiene interventions (p = 0.011). Patients with a lymphoma diagnosis were more likely to develop perioral scleroderma and chronic oral GvHD (cGvHD) (p = 0.045). Oral acute GvHD (aGvHD) was seen in 26 patients (49.1%). 21 (39.6%) patients developed cGvHD. GvHD of the tongue was seen in 21 (40%) patients. Oral mucositis was seen in only 5 patients (9.4%). Conditioning regimens with RT are more likely to induce oral aGvHD. The tongue is often affected by GvHD.