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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
Tel. +41 91 820 0300 - Fax +41 91 820 0302 - info [at] irb [dot] usi [dot] ch

T Cell Development

Fabio Grassi, Group Leader

Elisa Civanelli, Benedetta De Ponte Conti , Tanja Rezzonico Jost, Lisa Perruzza, Matteo Raneri, Morena Scantamburlo

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 function of the immune system. 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) and luminal secretion guarantee mucosal protection by entrapping microorganism in the mucus, neutralizing invading pathogens and microbial inflammatory compounds. Adenosine triphosphate (ATP) is a ubiquitous extracellular messenger, which activates purinergic receptors in the plasma membrane termed P2 receptors. The P2X7 receptor subtype is an ATP-gated nonselective cationic channel expressed in a variety of cell types. In T cells protracted receptor stimulation leads to cell death. P2X7 plays a crucial role in regulating Tfh cells abundance and thereby T dependent secretory IgA (SIgA) and microbiota composition. We investigate different aspects of the extracellular ATP (eATP)/P2X7 axis in regulating host/microbiota mutualism in the gut.