P38 as signaling hub for NLRP1 activation in the skin
—Inflammasomes integrate different cues of infection or cellular damage to trigger an inflammatory response. The Nucleotide-binding domain and leucine-rich repeat containing protein 1 (NLRP1) expressed in Keratinocytes coordinates inflammation in the skin. A recent study by ImmunoSensation² scientists the University of Bonn in cooperation with colleagues at the University of Melbourne and the Boston Children’s Hospital has now identified p38 as the key…
Hemophilia: Training the immune system to be tolerant
—Hemophilia A is the most common severe form of hemophilia. It affects almost exclusively males. The disease can usually be treated well, but not for all sufferers. Researchers at the cluster of Excellence ImmunoSensation² now elucidated an important mechanism that is crucial for making the therapy effective. The results could help better tailor treatment to patients. They have already been published online in a preliminary version; the final version will soon be published in the "Journal of Clinical Investigation."
Dendritic cells use centrosomes to enhance their motility
—A migration mechanism previously known only from metastatic cancer cells has now also been demonstrated for leukocytes. This is the conclusion of a recent study led by researchers from ImmunoSensation² at the University of Bonn. According to the study, centrioles of dendritic cells proliferate and cluster together. This makes it easier for the cells to maintain their direction and thus migrate more quickly to the lymph nodes, where they activate other immune cells. The results have now been…
—Toll like receptors (TLRs) are an integral part of our innate immune defense, as they recognize various pathogen associated molecular patterns (PAMPS). The TLR family members 7 and 8 are capable of detecting RNA molecules, actually in order to alert for viral infections. But both receptors may also be stimulated by artificial RNA molecules. A commonly known agonist of TLR7 and TLR8 is the 18s-rRNA derived oligonucleotide RNA63. It has been shown, that the receptor specificity of RNA63 is strongly dependent on the RNA…
—Our own immune system can become the enemy when mechanisms that are actually protective get out of control. In ANCA-associated vasculitis, excessive inflammatory reactions lead to pulmonary hemorrhages that can be fatal if left untreated. Researchers at ImmunoSensation², together with colleagues from Germany, the Netherlands, Switzerland and England, have deciphered a mechanism in mice and patients that leads to the severe disease. The results are now published in the Journal of Experimental Medicine.
Structure of periplasmic TRAP transporter revealed
—Elevator Tripartite ATP-independent periplasmic (TRAP) transporters are found among various bacteria and archaea. They are situated in the periplasmic space and act as transport proteins for organic acids and related molecules. Though TRAP transporters are known to harbor two transmembrane domains and one soluble substrate-binding protein domain, until now the exact molecular structure remained elusive. Scientists of the excellence cluster ImmunoSensation² at the University of Bonn in…
Cross-validation of distance measurements in proteins
—In order to investigate intermolecular distances, conformational changes or structural heterogeneity of biological molecules, two different methods are widely used: Pulsed electron-electron double resonance spectroscopy (PELDOR/DEER) and single-molecule Förster resonance energy transfer spectroscopy (smFRET). Scientists of the excellence cluster ImmunoSensation² at the University of Bonn and of the Ludwig-Maximilians-Universität (LMU) Munich have now compared the accuracy of the two methods. The study…
Covid-19: Immune response hampered by low availability of ketone bodies
—In Covid-19 patients, the metabolism produces energy-rich ketone bodies in insufficient amounts. However, these energy carriers are needed by both helper and killer T-cells in order to fight the virus effectively. Perhaps this finding explains why some people become much more seriously ill than others. A study led by ImmunoSensation² member Prof. Christoph Wilhelm at least points in this direction. The results have now been published in the journal Nature. They also give hope for new therapeutic…
Inosine enhances energy consumption in brown fat tissue
—A study led by ImmunoSensation2 member Prof. Alexander Pfeiffer at the University Hospital Bonn identified a molecule - the purine inosine - that boosts fat burning in brown adipocytes. The mechanism was discovered in mice, but probably exists in humans as well: If a transporter for inosine is less active, the mice remain significantly leaner despite a high-fat diet. The study, which also involved researchers from the University of Leipzig and the University Medical Center Hamburg-Eppendorf,…
