Set Theory for Immune Cells
Lichtenberg-Professor Dr. Max Löhning and colleagues at the Charité, Berlin, have demonstrated that immune cells can 'remember' numbers. In the future, it may thus be possible to influence the intensity of a specific immune reaction. The results of their study have been published in the current edition of the journal Immunity.
Immunologists from the Charité – Universitätsmedizin Berlin and the Deutsches Rheuma-Forschungszentrum led by Lichtenberg Professor Dr. Max Löhning, Deputy Director of the
Research Center for ImmunoScience of the Charité, have been conducting research on the maturation and differentiation of T-helper cells. These cells secrete messenger substances, so-called cytokines, that serve to regulate immune responses. The research group has now succeeded in demonstrating that a T-helper cell at the time of its initial activation, for example by way of infection, not only 'learns' which cytokine it needs to produce, but also in which quantity. T-helper cells stably retain this "quantitative cytokine memory". If the infection is conquered, some of the T-helper cells transforme into long-lived memory T cells. Whenever a new infection emerges these memory T cells are activated and again release the same predetermined quantity of cytokine. It was already known that T cells can produce different quantities of a messenger substance, but it was assumed that these were randomly distributed and could not be stably 'remembered' in the individual cells. The researchers also identified a key factor with respect to the retention of "quantitative cytokine memory" of individual T cells: a transcription factor that exists in a specific quantity in the nucleus of each cell and manifests as a "swimming manufacturing specification. If the transcription factor is present in large quantities, a large quantity of cytokine will also be produced, and vice-versa. The cells stably retain their respective levels of the transcription factor and thus also their cell-specific production amounts of the cytokine.
In the context of an immune response, both T-helper cells producing small quantities of a certain cytokine as well as those producing larger quantities are present. "We assume that in this way a fine adjustment of the immune reaction is achieved, because while the messenger substances are useful, they can cause physical damage in higher doses. At worst, the body's own structures are attacked or otherwise harmless substances are antagonized", is how Professor Löhning explains the study's findings. "Such occurrences are caused by an overreaction of the immune system. The recently discovered level of quantitative regulation may make it possible to foster only weakly reacting immune cells, and in turn, to attenuate the overall immune response. Conversely, when combating cancer cells and many infections, we would increase the number of highly active immune cells in a targeted manner", he added.
Publication
Caroline Helmstetter, Michael Flossdorf, Michael Peine, Andreas Kupz, Jinfang Zhu, Ahmed N. Hegazy, Maria A. Duque-Correa, Qin Zhang, Yevhen Vainshtein, Andreas Radbruch, Stefan H. Kaufmann, William E. Paul, Thomas Höfer und Max Löhning. Individual T helper cells have a quantitative cytokine memory. Immunity, January 2015. doi:10.1016/j.immuni.2014.12.018.
Contact
Univ.-Prof. Dr. Max Löhning
Lichtenberg-Professur für Experimentelle Immunologie
Charité - Universitätsmedizin Berlin (CCM)
Med. Klinik m. S. Rheumatologie u. Klinische Immunologie
Deutsches Rheuma-Forschungszentrum (DRFZ)
Charitéplatz 1, D-10117 Berlin
Tel.: +49 (0)30 28460-760/-711
Über diesen neu entdeckten Mechanismus zur Regulierung der Produktionsmengen von Zytokinen könnte es künftig möglich sein, Immunreaktionen gezielt zu beeinflussen. Im Fall von Autoimmunerkrankungen oder Allergien würden beispielsweise solche Immunzellen gefördert, die nur geringe Mengen an Botenstoffen ausschütten, um die Immunantwort insgesamt abzumildern. Beim Kampf gegen Krebszellen und viele Infektionen hingegen würde die Anzahl hoch aktiver Immunzellen erhöht. Die Ergebnisse der Studie sind in der aktuellen Ausgabe der Fachzeitschrift
Immunity veröffentlicht.
Originalpublikation:
"Individual T helper cells have a quantitative cytokine memory", Immunity 42, 20. Januar 2015. Caroline Helmstetter, Michael Flossdorf, Michael Peine, Andreas Kupz, Jinfang Zhu, Ahmed N. Hegazy, Maria A. Duque-Correa, Qin Zhang, Yevhen Vainshtein, Andreas Radbruch, Stefan H. Kaufmann, William E. Paul, Thomas Höfer und Max Löhning. doi:10.1016/j.immuni.2014.12.018
Kontakt
Univ.-Prof. Dr. Max Löhning
Lichtenberg-Professur für Experimentelle Immunologie
Charité - Universitätsmedizin Berlin (CCM)
Med. Klinik m. S. Rheumatologie u. Klinische Immunologie
Deutsches Rheuma-Forschungszentrum (DRFZ)
Charitéplatz 1, D-10117 Berlin
Tel.: +49 (0)30 28460-760/-711
The Volkswagen Foundation combines support both for individual researchers as well as institutions via the funding initiative 'Lichtenberg Professorships'. Outstanding (young) researchers are offered a tenure-track at a university of their choice in Germany, enabling them to carry out independent research in innovative and interdisciplinary areas for longer periods of time. Deadline for application is June 2, 2015. For more information, please see
Lichtenberg Professorships.
Retrieved from Charité Berlin, press release 2015.01.21:
http://www.charite.de/en/charite/press/press_reports/artikel/detail/mengenlehre_fuer_immunzellen