title: T-cell Expression of IL10 Is Essential for Tumor Immune Surveillance in the Small Intestine.
abstract: IL10 is attributed with immune-suppressive and anti-inflammatory properties, which could promote or suppress cancer in the gastrointestinal tract. Loss of IL10 exacerbates colonic inflammation, leading to colitis and cancer. Consistent with this, transfer of IL10-competent regulatory T cells (Treg) into mice with colitis or hereditary polyposis protects against disease, while IL10-deficient mice are predisposed to polyposis with increased colon polyp load. Little is known about the protective or pathogenic function of IL10 in cancers of the small intestine. We found CD4(+) T cells and CD4(+) Foxp3(+) Tregs to be the major sources of IL10 in the small intestine and responsible for the increase in IL10 during polyposis in the APC(Δ468) mouse model of hereditary polyposis. Targeted ablation of IL10 in T cells caused severe IL10 deficiency and delayed polyp growth. However, these polyps progressively lost cytotoxic activity and eventually progressed to cancer. Several observations suggested that the effect was due to the loss of IFNγ-dependent immune surveillance. IL10-incompetent CD4(+) T cells failed to secrete IFNγ when stimulated with polyp antigens and were inefficient in T-helper-1 (TH1) commitment. By contrast, the TH17 commitment was unaffected. These findings were validated using mice whose T cells overexpress IL10. In these mice, we observed high intra-polyp cytotoxic activity and attenuation of polyposis. Thus, expression of IL10 by T cells is protective and required for immune surveillance in the small intestine.
authors: Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Kristen L
authors: KL
authors: Dennis
authors: Departments of Immunology and Surgery, Mayo College of Medicine, Mayo Clinic, Rochester, Minnesota.
authors: Abdulrahman
authors: A
authors: Saadalla
authors: Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Nichole R
authors: NR
authors: Blatner
authors: Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Shuya
authors: S
authors: Wang
authors: Committee on Immunology, Department of Medicine, The University of Chicago, Chicago, Illinois.
authors: Vysak
authors: V
authors: Venkateswaran
authors: Committee on Immunology, Department of Medicine, The University of Chicago, Chicago, Illinois.
authors: Fotini
authors: F
authors: Gounari
authors: Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California.
authors: Hilde
authors: H
authors: Cheroutre
authors: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors: Casey T
authors: CT
authors: Weaver
authors: Institute for Immunology, Technical University Dresden, Dresden, Germany.
authors: Axel
authors: A
authors: Roers
authors: Department of Microbiology and Immunology, School of Medicine, University of Louisville, Louisville, Kentucky.
authors: Nejat K
authors: NK
authors: Egilmez
authors: Departments of Immunology and Surgery, Mayo College of Medicine, Mayo Clinic, Rochester, Minnesota. khazaie@mayo.edu.
authors: Khashayarsha
authors: K
authors: Khazaie
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D006801:Humans; D007157:Immunologic Surveillance; D016753:Interleukin-10 / Q000276:immunology*; D007414:Intestinal Neoplasms / Q000276:immunology*; D007421:Intestine, Small / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D016753:Interleukin-10