Giulia Fornasa, PhD
,
European institute of oncology, Milan, Italy
Maria Rescigno, Prof
,
European Institute of Oncology, Milano, Italy
Katerina Tsilingiri, PhD
,
European Institute of Oncology, Milano, Italy
Flavio Caprioli, MD, PhD
,
Ospedale Maggiore Policlinico di Milano, Milan, Italy
Fiorenzo Botti, MD
,
Ospedale Maggiore Policlinico di Milano, Milan, Italy
Marina Mapelli, PhD
,
European Institute of Oncology, Milan, Italy
Stephan Meller, MD
,
University of Duesseldorf, Duesseldorf, Germany
Andreas Kislat
,
University of Duesseldorf, Duesseldorf, Germany
Giuseppe Viale, MD
,
European Institute of Oncology, Milan, Italy
Bernhard Homey, MD
,
University of Duesseldorf, Duesseldorf, Germany
Antonio Di Sabatino, MD
,
3First Department of Medicine, St. Matteo Hospital, University of Pavia, Pavia, Italy
Giuseppe Diaferia, PhD
,
European Institute of Oncology, Milan, Italy
Alessandro Gori, PhD
,
CNR, Istituto di Chimica del Riconoscimento Molecolare, Milan, Italy
Renato Longhi, PhD
,
CNR, Istituto di Chimica del Riconoscimento Molecolare, Milan, Italy
Giuseppe Penna
,
European Institute of Oncology, Milan, Italy
Thymic stromal lymphopoietin is an IL-7 like cytokine produced by epithelial and stromal cells. TSLP has been shown to play a major role in homeostatic immune responses, mainly in the thymus and the gut. Conversely, overexpression of TSLP and TSLP-induced Th2 responses are also associated with allergic manifestations and with cancer progression. In humans, two isoforms of TSLP exist, the “long” and the “short” isoform. Even though the most well characterized form of TSLP is the long one, we found that the short isoform, always ignored, is readily expressed in various tissues.
The short isoform is the only one expressed in healthy intestinal and skin tissue and it is downregulated in inflamed tissues. It also exerts anti-inflammatory activities by inhibiting the ability of DCs to respond to bacteria and to produce inflammatory cytokines. Consistently short TSLP administration in mice dampens inflammation after endoxin-shock and ameliorates experimental colitis. The long isoform is expressed only in disease conditions like ulcerative colitis and atopic dermatitis and is the isoform responsible for the induction of inflammatory Th2-like responses.
In conclusion we showed that they have opposite expression patterns and elicit distinct immunological responses, probably explaining the dual role of the TSLP in the literature.
