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PMID: 20308560 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 107 ·No. 14 ·2010-04-06 ·Pages 6430-5

Blatner NR, Bonertz A, Beckhove P, Cheon EC, Krantz SB, Strouch M, Weitz J, Koch M, Halverson AL, Bentrem DJ, Khazaie K

Abstract

T-regulatory cells (Treg) and mast cells (MC) are abundant in colorectal cancer (CRC) tumors. Interaction between the two is known to promote immune suppression or loss of Treg functions and autoimmunity. Here, we demonstrate that in both human CRC and murine polyposis the outcome of this interaction is the generation of potently immune suppressive but proinflammatory Treg (DeltaTreg). These Treg shut down IL10, gain potential to express IL17, and switch from suppressing to promoting MC expansion and degranulation. This change is also brought about by direct coculture of MC and Treg, or culture of Treg in medium containing IL6 and IL2. IL6 deficiency in the bone marrow of mice susceptible to polyposis eliminated IL17 production by the polyp infiltrating Treg, but did not significantly affect the growth of polyps or the generation of proinflammatory Treg. IL6-deficient MC could generate proinflammatory Treg. Thus, MC induce Treg to switch function and escalate inflammation in CRC without losing T-cell-suppressive properties. IL6 and IL17 are not needed in this process.

MeSH Terms

Animals Coculture Techniques Colorectal Neoplasms/immunology Humans Interleukins/deficiency,immunology Mast Cells/immunology Mice Mice, Knockout T-Lymphocytes, Helper-Inducer/immunology T-Lymphocytes, Regulatory/immunology

Chemicals

Interleukins

Authors & Affiliations

11 authors, click to expand affiliations / ORCID

Blatner Nichole R

Division of Gastroenterology and Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.

Bonertz Andreas

Beckhove Philipp

Cheon Eric C

Krantz Seth B

Strouch Matthew

Weitz Juergen

Koch Moritz

Halverson Amy L

Bentrem David J

Khazaie Khashayarsha

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Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

1091-6490

DOI

10.1073/pnas.0913683107

Published

2010-04-06

Epub

2010-00-22

Pages

6430-5

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC2851977

Subset

Grants

NCRR NIH HHS · UL1 RR025741 · United States

Corrections

ErratumIn

External Links

PubMed source DOI: 10.1073/pnas.0913683107 PMC Full Text View journal details

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In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction.

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