Cell-Intrinsic NF-κB Activation Is Critical for the Development of Natural Regulatory T Cells in Mice

regulatory T (Treg) cells develop in the thymus and represent a mature T cell subpopulation critically involved in maintaining peripheral tolerance. The differentiation of Treg cells in the thymus requires T cell receptor (TCR)/CD28 stimulation along with cytokine-promoted Foxp3 induction. TCR-mediated nuclear factor kappa B (NF-κB) activation seems to be involved in differentiation of Treg cells because deletion of components of the NF-κB signaling pathway, as well as of NF-κB transcription factors, leads to markedly decreased Treg cell numbers in thymus and periphery. thymic Treg precursors and their further differentiation into mature Treg cells. Treg cell development could neither be completely rescued by the addition of exogenous Interleukin 2 (IL-2) nor by the presence of wild-type derived cells in adoptive transfer experiments. However, peripheral NF-κB activation appears to be required for IL-2 production by conventional T cells, thereby participating in Treg cell homeostasis. Moreover, pharmacological NF-κB inhibition via the IκB kinase β (IKKβ) inhibitor AS602868 led to markedly diminished thymic and peripheral Treg cell frequencies.Our results indicate that Treg cell-intrinsic NF-κB activation is essential for thymic Treg cell differentiation, and further suggest pharmacological NF-κB inhibition as a potential therapeutic approach for manipulating this process

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Internet-based syndromic monitoring of acute respiratory illness in the general population of Germany, weeks 35/2011 to 34/2012

In March 2011, the German sentinel surveillance system for influenza (Arbeitsgemeinschaft Influenza (AGI)) was complemented by an Internet-based syndromic monitoring system (GrippeWeb) for acute respiratory infections (ARI) and influenza-like-illness (ILI). To assess representativeness of GrippeWeb participants, key demographic variables and lifetime prevalence of asthma and diabetes were compared with data from the general population of Germany. To ‘validate’ GrippeWeb, we compared weekly ARI and medically attended ARI (MAARI) rates, generated between weeks 35/2011 and 34/2012, with AGI MAARI rates and overlaid GrippeWeb ILI rates with the number of positive influenza samples obtained by the AGI. GrippeWeb had high weekly participation rates (62% of participants reported in ≥90% of possible weeks). Although it varied by age group, participants reported a mean of between 1.3 and 6.0 ARI episodes and between 0.1 and 2.4 ILI episodes during the study year. Estimated GrippeWeb MAARI incidence was very similar to the AGI MAARI incidence and influenza circulation was reflected well in the GrippeWeb ILI rates. GrippeWeb became a reliable monitoring system shortly after implementation, capturing the burden of ARI and ILI at general population level. The high degree of agreement between GrippeWeb’s and AGI’s MAARI data lends support to the validity of both systems

Internet-based syndromic monitoring of acute respiratory illness in the general population of Germany, weeks 35/2011 to 34/2012

In March 2011, the German sentinel surveillance system for influenza (Arbeitsgemeinschaft Influenza (AGI)) was complemented by an Internet-based syndromic monitoring system (GrippeWeb) for acute respiratory infections (ARI) and influenza-like-illness (ILI). To assess representativeness of GrippeWeb participants, key demographic variables and lifetime prevalence of asthma and diabetes were compared with data from the general population of Germany. To ‘validate’ GrippeWeb, we compared weekly ARI and medically attended ARI (MAARI) rates, generated between weeks 35/2011 and 34/2012, with AGI MAARI rates and overlaid GrippeWeb ILI rates with the number of positive influenza samples obtained by the AGI. GrippeWeb had high weekly participation rates (62% of participants reported in ≥90% of possible weeks). Although it varied by age group, participants reported a mean of between 1.3 and 6.0 ARI episodes and between 0.1 and 2.4 ILI episodes during the study year. Estimated GrippeWeb MAARI incidence was very similar to the AGI MAARI incidence and influenza circulation was reflected well in the GrippeWeb ILI rates. GrippeWeb became a reliable monitoring system shortly after implementation, capturing the burden of ARI and ILI at general population level. The high degree of agreement between GrippeWeb’s and AGI’s MAARI data lends support to the validity of both systems

Pathways to cancer counselling centres: How do people become aware of them? A qualitative study with people seeking advice and those referring them

Schranz M, Bayer O, Xylaender M, et al. Wege in Krebsberatungsstellen: Wie werden Menschen darauf aufmerksam? Eine qualitative Studie mit Ratsuchenden und Zuweisenden. Onkologe. 2022.Background Outpatient cancer counselling centres (OCCC; in German Krebsberatungsstellen [KBS]) offer psychological, social and sociolegal support for people with cancer and their relatives, who are confronted not only with physical but also with psychosocial stress as a result of the disease. Research question How do people become aware of outpatient cancer counselling centres? Methods In a nationwide study, guided qualitative interviews were conducted with people seeking advice (cancer patients and relatives) and referrers (health care providers who refer to OCCC). The interviews with those seeking advice were conducted face-to-face and those with referrers by telephone. The data were analysed using content analysis according to Mayring. Results In all, 43 people seeking advice and 30 referrers were interviewed. A total of 31 h of audio material was recorded. From the respondents' point of view, flyers, information brochures and internet platforms are important sources for making patients and their relatives aware of OCCC. In addition to public relations, the personal approach in the clinical and non-clinical care system and in the social setting is of central importance. Some referrers address OCCC routinely, while others only do so when patients or relatives explicitly express a need for counselling. Conclusions In the medical sector, more attention could and should be drawn to OCCC as a helpful outpatient counselling setting. Closer cooperation between OCCC and general practitioners, oncologists and psycho-oncology services should be sought. Targeted and needs-oriented information can draw attention to the support offered by OCCC and thus improve the care of cancer patients.Hintergrund Ambulante Krebsberatungsstellen (KBS) bieten psychologische, soziale und sozialrechtliche Unterstützung für an Krebs erkrankte Menschen und Angehörige an, die infolge der Erkrankung nicht nur mit körperlichen, sondern auch mit psychosozialen Belastungen konfrontiert werden. Fragestellung Wie werden Menschen auf ambulante Krebsberatungsstellen aufmerksam? Methoden In einer deutschlandweiten Studie wurden leitfadengestützte qualitative Interviews mit Ratsuchenden (Krebspatient/innen und Angehörige) und Zuweisenden (Gesundheitsversorger/innen, die an KBS verweisen) geführt. Die Befragungen der Ratsuchenden erfolgten im persönlichen Gespräch, die der Zuweisenden telefonisch. Ausgewertet wurde inhaltsanalytisch nach Mayring. Ergebnisse Es wurden 43 Ratsuchende und 30 Zuweisende befragt. Insgesamt entstanden 31 h Audiomaterial. Aus Sicht der Befragten sind Flyer, Infobroschüren und Internetplattformen wichtige Quellen, um Patient/innen und deren Angehörige auf KBS aufmerksam zu machen. Neben der Öffentlichkeitsarbeit ist die persönliche Ansprache im klinischen wie nicht-klinischen Versorgungssystem und im sozialen Umfeld von zentraler Bedeutung. Manche Zuweisenden sprechen KBS routinemäßig an, andere erst bei explizit von Patient/innen oder Angehörigen geäußertem Beratungsbedarf. Schlussfolgerungen Im medizinischen Sektor könnte und sollte noch mehr auf KBS als hilfreiches ambulantes Beratungssetting hingewiesen werden. Eine engere Zusammenarbeit der KBS mit Hausärzt/innen, Onkolog/innen und psychoonkologischen Diensten ist anzustreben. Gezielte und bedarfsgerechte Informationen können auf das Unterstützungsangebot durch eine KBS hinweisen und so die Versorgung von Krebspatient/innen verbessern

Ways to Cancer Counseling Centers: How do People Become Aware of these Centers?

Schranz M, Bayer O, Xyländer M, et al. Ways to Cancer Counseling Centers: How do People Become Aware of these Centers? In: ONCOLOGY RESEARCH AND TREATMENT. Vol 43. Basel: Karger; 2020: 180