Zerebraler Krampfanfall und Lungenrundherd unter Immunsuppression

Zusammenfassung: Die Zahl der Patienten, die eine immunsuppressive Therapie erhalten, ist steigend. Demzufolge sollte bei unklaren pulmonalen Prozessen mit oder ohne zerebrale Beteiligung neben einem Bronchialkarzinom immer auch an eine opportunistische systemische Infektion gedacht werden. Als ein Beispiel dafür wird hier über eine systemische Nokardiose berichtet. Da die klinische Symptomatik der Nokardiose völlig unspezifisch ist, wird sie oft nicht oder zu spät differenzialdiagnostisch in Erwägung gezogen. Nokardien kommen ubiquitär vor. Sie gelangen v.a. via Inhalation in den menschlichen Körper. Unterschieden wird die lokalisierte von der systemischen (disseminierten) Infektion, die mit einer hohen Mortalität, insbesondere bei immunsupprimierten Patienten, verbunden ist. In der Regel besteht die Therapie der Nokardiose in einer Langzeitantibiotikagab

Ascl2-Dependent Cell Dedifferentiation Drives Regeneration of Ablated Intestinal Stem Cells

Ablation of LGR5+ intestinal stem cells (ISCs) is associated with rapid restoration of the ISC compartment. Different intestinal crypt populations dedifferentiate to provide new ISCs, but the transcriptional and signaling trajectories that guide this process are unclear, and a large body of work suggests that quiescent “reserve” ISCs contribute to regeneration. By timing the interval between LGR5+ lineage tracing and lethal injury, we show that ISC regeneration is explained nearly completely by dedifferentiation, with contributions from absorptive and secretory progenitors. The ISC-restricted transcription factor ASCL2 confers measurable competitive advantage to resting ISCs and is essential to restore the ISC compartment. Regenerating cells re-express Ascl2 days before Lgr5, and single-cell RNA sequencing (scRNA-seq) analyses reveal transcriptional paths underlying dedifferentiation. ASCL2 target genes include the interleukin-11 (IL-11) receptor Il11ra1, and recombinant IL-11 enhances crypt cell regenerative potential. These findings reveal cell dedifferentiation as the principal means for ISC restoration and highlight an ASCL2-regulated signal that enables this adaptive response

Tritiated thymidine autoradiographic study on the influence of sensory and sympathetic innervation on periodontal wound healing in the rat

Understanding of wound healing mechanisms is important in designing preventive and therapeutic approaches to inflammatory periodontal diseases, which are a major cause of dental morbidity. In this study, cell proliferation was assessed after an experimental gingival wound; this was preceded by either resection of 3 mm of the inferior alveolar nerve, total extirpation of the superior cervical ganglion, trauma to those structures or sham operations. At different times, animals were pulsed with 0.5 [mu] Ci/g body weight of tritiated thymidine; histological sections were processed for quantitative autoradiography of different compartments of the peridontium. Wounding led to a significant increase in cell proliferation in the epithelial layer, the fibroblast compartment and the periodontal ligament, but not in the alveolar crest compartment. Sympathetic denervation significantly enhanced this response in the epithelial layer, the fibroblast compartment and the alveolar crest, whereas sensory denervation only modified the response in the fibroblast layer. Thus it appears that sympathetic innervation plays an important role in the regulation of cell proliferation in the periodontium and that pharmacological modulation of sympathetic activity should be further studied as a therapeutic approach in periodontal disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28886/1/0000722.pd

A highly tilted binding mode by a self-reactive T cell receptor results in altered engagement of peptide and MHC

A TCR derived from a patient with relapsing-remitting multiple sclerosis engages the self-peptide myelin basic protein in the context of HLA-DQ1 in a very unusual way

Tracing Functional Antigen-Specific CCR6+ Th17 Cells after Vaccination

BACKGROUND: The function of T helper cell subsets in vivo depends on their location, and one hallmark of T cell differentiation is the sequential regulation of migration-inducing chemokine receptor expression. CC-chemokine receptor 6 (CCR6) is a trait of tissue-homing effector T cells and has recently been described as a receptor on T helper type 17 (Th17) cells. Th17 cells are associated with autoimmunity and the defence against certain infections. Although, the polarization of Th cells into Th17 cells has been studied extensively in vitro, the development of those cells during the physiological immune response is still elusive. METHODOLOGY/PRINCIPAL FINDINGS: We analysed the development and functionality of Th17 cells in immune-competent mice during an ongoing immune response. In naïve and vaccinated animals CCR6(+) Th cells produce IL-17. The robust homeostatic proliferation and the presence of activation markers on CCR6(+) Th cells indicate their activated status. Vaccination induces antigen-specific CCR6(+) Th17 cells that respond to in vitro re-stimulation with cytokine production and proliferation. Furthermore, depletion of CCR6(+) Th cells from donor leukocytes prevents recipients from severe disease in experimental autoimmune encephalomyelitis, a model for multiple sclerosis in mice. CONCLUSIONS/SIGNIFICANCE: In conclusion, we defined CCR6 as a specific marker for functional antigen-specific Th17 cells during the immune response. Since IL-17 production reaches the highest levels during the immediate early phase of the immune response and the activation of Th17 cells precedes the Th1 cell differentiation we tent to speculate that this particular Th cell subset may represent a first line effector Th cell subpopulation. Interference with the activation of this Th cell subtype provides an interesting strategy to prevent autoimmunity as well as to establish protective immunity against infections

Th17 Cells Induce Ectopic Lymphoid Follicles in Central Nervous System Tissue Inflammation

Ectopic lymphoid follicles are hallmarks of chronic autoimmune inflammatory diseases such as multiple sclerosis (MS), rheumatoid arthritis, Sjögren's syndrome, and myasthenia gravis. However, the effector cells and mechanisms that induce their development are unknown. Here we showed that in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, Th17 cells specifically induced ectopic lymphoid follicles in the central nervous system (CNS). Development of ectopic lymphoid follicles was partly dependent on the cytokine interleukin 17 (IL-17) and on the cell surface molecule Podoplanin (Pdp), which was expressed on Th17 cells, but not on other effector T cell subsets. Pdp was also crucial for the development of secondary lymphoid structures: Pdp-deficient mice lacked peripheral lymph nodes and had a defect in forming normal lymphoid follicles and germinal centers in spleen and lymph node remnants. Thus, Th17 cells are uniquely endowed to induce tissue inflammation, characterized by ectopic lymphoid follicles within the target organ

(Same)-sex in the City: urbanisation and LGBTI rights expansion

Despite the notable successes of lesbian, gay, bisexual, transgender and intersex (LGBTI) activism in the region, individual European countries have varied considerably in the extent and speed with which they have adopted legislation to recognise the rights of their LGBTI citizens. Scholars have often turned to modernisation theory to explain these variable outcomes and argue that high levels of national wealth are an important factor in the success of LGBTI movements. Although the correlation between modernity, economic development and tolerance of LGBTI lifestyles is often treated as a truism in the literature, scholars have paid less attention to the precise mechanisms by which the complex processes associated with modernisation facilitate policy change. Drawing on the classic works of both modernisation theory and gay and lesbian history, we examine a less explored route by which modernisation leads to the expansion of LGBTI rights. Specifically, we posit that urbanisation facilitates the adoption of rights policies by strengthening LGBTI movements and enhancing their political effectiveness. To test this proposition, we use event history analysis and an original dataset that contains measures for institutional, cultural, economic and movement variables, as well as measures of urbanisation in 44 European countries between 1980 and 2015. Our findings support the contention that urbanisation has a strong effect on the formation of LGBTI movement organisations as well as the speed with which European states adopt both same‐sex union and anti‐discrimination legislation. The relationship between urbanisation and rights expansion persists even after controlling for a country's level of wealth, religious adherence and the influence of European institutions and norms

A presynaptic endosomal trafficking pathway controls synaptic growth signaling

Association of Nwk with SNX16 promotes down-regulation of synaptic growth signaling at the interface between early and recycling endosomes

Class II MHC Self-Antigen Presentation in Human B and T Lymphocytes

Human CD4[superscript +] T cells process and present functional class II MHC-peptide complexes, but the endogenous peptide repertoire of these non-classical antigen presenting cells remains unknown. We eluted and sequenced HLA-DR-bound self-peptides presented by CD4[superscript +] T cells in order to compare the T cell-derived peptide repertoire to sequences derived from genetically identical B cells. We identified several novel epitopes derived from the T cell-specific proteome, including fragments of CD4 and IL-2. While these data confirm that T cells can present peptides derived from the T-cell specific proteome, the vast majority of peptides sequenced after elution from MHC were derived from the common proteome. From this pool, we identified several identical peptide epitopes in the T and B cell repertoire derived from common endogenous proteins as well as novel endogenous epitopes with promiscuous binding. These findings indicate that the endogenous HLA-DR-bound peptide repertoire, regardless of APC type and across MHC isotype, is largely derived from the same pool of self-protein.National Institutes of Health (U.S.) (grant P01AI039671)National Institutes of Health (U.S.) (P01AI045757