When the right microorganisms are at work, immune cells involved in the development of autoimmune illnesses like psoriasis, multiple sclerosis and arthritis, can develop anti-inflammatory properties. Scientists at Charité — Universitätsmedizin Berlin and the Institute for Research in Biomedicine, Bellinzona, Switzerland, have now made this discovery. The scientists have demonstrated that particular fungi activate the immune cells involved in the development of certain illnesses, whereas other microorganisms, in particular bacteria that are found naturally on our skin, lend an anti-inflammatory function to them.
“This not only demonstrates that the composition of our microflora has a decisive role in the development of chronic illnesses, but also that the key cells causing illness can develop an anti-inflammatory ‘twin’,” explained Dr. Christina Zielinski, first author of the study.
Their work is published in the current issue of the scientific journal Nature.
The 32-year old researcher from the Dermatology and Allergology Clinic at Charité and Berlin-Brandenburg School for Regenerative Therapies, and her colleagues identified the basic signals that contribute to whether or not a pathogenic or anti-inflammatory immune cell develops. It then emerged that interleukin 1b, one of the body’s own immune system hormones, works like a molecular switch. Its presence trains immune cells during autoimmune occurrences to function destructively and to release inflammatory messenger substances. Its absence, on the other hand, allows the immune cells to mature into anti-inflammatory counterparts. Interestingly, it is our own body’s microorganisms that decide whether interleukin 1b is produced and therefore which mode is selected.
This observation prompted the scientists to also look for patients suffering from an overproduction of interleukin 1b, which is the case in the so-called auto-inflammatory syndromes (e.g. CAPS, Muckle-Wells, or Schnitzler Syndromes). These patients, especially children, suffer from multiple symptoms like fever, arthritis, and skin rashes. The exact development of these diseases is, however, to a large extent unexplained. Researchers tested whether a therapy of antibodies that block interleukin 1b can generate anti-inflammatory potential in the immune cells. In fact, after the introduction of this therapy the immune cells produced inflammation-retardant messengers. They even developed a memory to release the messenger substances over long time periods.
“I am convinced that an imbalance in our microbial microflora has a decisive influence on the development of chronic inflammatory illnesses like rheumatism, Morbus Crohn and psoriasis. Our organism is composed of ten times more microbial cells than our body’s own cells. Keeping this in check is not easy. Interleukin 1b is now turning out to be a decisive molecular switch, which the microbes use to dictate between healthy or sick,” says Dr. Christina Zielinski. She sees great potential in the therapy of inflammatory diseases by blocking this messenger substance. In contrast to other immune therapies this does not lead to a weakening of the immune system, but rather enables the cells instead to be anti-inflammatory if needed, without losing the ability to fight dangerous pathogens.
Journal Reference: Christina E. Zielinski, Federico Mele, Dominik Aschenbrenner, David Jarrossay, Francesca Ronchi, Marco Gattorno, Silvia Monticelli, Antonio Lanzavecchia, Federica Sallusto. Pathogen-induced human TH17 cells produce IFN-γ or IL-10 and are regulated by IL-1β. Nature, 2012; DOI: 10.1038/nature10957
