Publikationsdatum:
2018-07-27
Beschreibung:
Germline mutations in STK11 , which encodes the tumor suppressor liver kinase B1 (LKB1), promote Peutz–Jeghers syndrome (PJS), a cancer predisposition syndrome characterized by the development of gastrointestinal (GI) polyps. Here, we report that heterozygous deletion of Stk11 in T cells (LT het mice) is sufficient to promote GI polyposis. Polyps from LT het mice, Stk11 +/– mice, and human PJS patients display hallmarks of chronic inflammation, marked by inflammatory immune-cell infiltration, signal transducer and activator of transcription 3 (STAT3) activation, and increased expression of inflammatory factors associated with cancer progression [interleukin 6 (IL-6), IL-11, and CXCL2]. Targeting either T cells, IL-6, or STAT3 signaling reduced polyp growth in Stk11 +/ – animals. Our results identify LKB1-mediated inflammation as a tissue-extrinsic regulator of intestinal polyposis in PJS, suggesting possible therapeutic approaches by targeting deregulated inflammation in this disease.
Schlagwort(e):
Immunology, Medicine, Diseases
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Geologie und Paläontologie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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