Fabio Grassi, Group Leader
The human gastrointestinal (GI) tract is a complex ecological niche, in which all the three domains of life (Archaea, Bacteria and Eukarya) and Viruses co-exist in close association with the host. This complex microbial community, referred to as the gut microbiota, has co-evolved with the host in a mutualistic relationship that influences many physiological functions such as energy harvesting, development and immune system activity. The subtle equilibrium between the gut microbiota and the host is a key element in human health. In fact, alterations in the composition of the microbial community structure, termed dysbiosis, have been associated to an increasing number of medical conditions. Since the immune system and the gut microbiota start developing together at birth, it has been hypothesized that their co-evolution selects and maintains mutualistic or symbiotic microorganisms within the GI niche. Central in this homeostatic relationship is the local production of immunoglobulin A (IgA), which is the most copious Ig isotype produced by the human immune system. IgA interaction with the polymeric Ig receptor (pIgR) expressed in enterocytes and luminal secretion guarantee mucosal protection by neutralizing invading pathogens and microbial inflammatory compounds as well as intestinal function by selecting beneficial microbes. We investigate mechanisms regulating the secretory IgA response and repertoire that in turn might influence host physiology and pathophysiology by shaping microbiota composition.