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Interleukin-10 in the Control of Tum...

University of Michigan.

Interleukin-10 in the Control of Tumor Immunity and Autoimmunity.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Interleukin-10 in the Control of Tumor Immunity and Autoimmunity.
Author:	Wilke, Cailin Moira.
Description:	122 p.
Notes:	Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
Notes:	Adviser: Weiping Zou.
Contained By:	Dissertation Abstracts International72-08B.
Subject:	Biology, Molecular.
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3459086
ISBN:	9781124691961

Interleukin-10 in the Control of Tumor Immunity and Autoimmunity.
Wilke, Cailin Moira.

Interleukin-10 in the Control of Tumor Immunity and Autoimmunity. - 122 p.

Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .

Thesis (Ph.D.)--University of Michigan, 2011.

IL-10 is known as an immunosuppressive cytokine. However, we have identified an immune-stimulatory role of IL-10 in tumor immunity. Interestingly, the incidence of chemically-induced tumors, transplanted tumor growth, and lung foci are increased in IL-10-deficient (IL-10-/-) mice. This phenomenon is associated with increased myeloid-derived suppressor cells (MDSCs) and CD4+Foxp3+ regulatory T(reg) cells, along with decreased natural killer (NK) cells, CD8+ T cells and T cell effector cytokines in the IL-10-/- tumor microenvironment. IL-10-/- MDSCs express high levels of interleukin IL-1 and MHC, and efficiently induce Treg cells. Genetic and biological blockade of the IL-1 signaling pathway reduces tumor growth and partially rescues effector T cell tumor infiltration and function, and decreases tumor angiogenesis and Treg cell tumor infiltration. This indicates that endogenous IL-10 may stimulate tumor immunity through direct activation of effector T cells, suppression of MDSCs and MDSC-induced Tregs, and reduction of pro-tumor activity mediated by inflammatory cytokines. Thus, our data challenge the dogma that IL-10 is solely immune suppressive.

ISBN: 9781124691961Subjects--Topical Terms:

226919
Biology, Molecular.

Interleukin-10 in the Control of Tumor Immunity and Autoimmunity.
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100 1 $a Wilke, Cailin Moira. $3 531099
245 1 0 $a Interleukin-10 in the Control of Tumor Immunity and Autoimmunity.
300 $a 122 p.
500 $a Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
500 $a Adviser: Weiping Zou.
502 $a Thesis (Ph.D.)--University of Michigan, 2011.
520 $a IL-10 is known as an immunosuppressive cytokine. However, we have identified an immune-stimulatory role of IL-10 in tumor immunity. Interestingly, the incidence of chemically-induced tumors, transplanted tumor growth, and lung foci are increased in IL-10-deficient (IL-10-/-) mice. This phenomenon is associated with increased myeloid-derived suppressor cells (MDSCs) and CD4+Foxp3+ regulatory T(reg) cells, along with decreased natural killer (NK) cells, CD8+ T cells and T cell effector cytokines in the IL-10-/- tumor microenvironment. IL-10-/- MDSCs express high levels of interleukin IL-1 and MHC, and efficiently induce Treg cells. Genetic and biological blockade of the IL-1 signaling pathway reduces tumor growth and partially rescues effector T cell tumor infiltration and function, and decreases tumor angiogenesis and Treg cell tumor infiltration. This indicates that endogenous IL-10 may stimulate tumor immunity through direct activation of effector T cells, suppression of MDSCs and MDSC-induced Tregs, and reduction of pro-tumor activity mediated by inflammatory cytokines. Thus, our data challenge the dogma that IL-10 is solely immune suppressive.
520 $a The mechanistic link between IL-10 and Th17 cells in autoimmune disease remains poorly understood. We have therefore examined the relationship of IL-10 to Th17 cells in both mouse and human autoimmune models. IL- -/- mice are susceptible to development of chronic enterocolitis. We have observed spontaneous systemic increases in Th17 cells in IL-10 -/- mice. IL-10-/- dendritic cells (DC) produce more IL-1 than IL-+/+ counterparts and are more powerful inducers of Th17 cells; this effect is abrogated upon IL-1 receptor (IL-1 R) blockade. In vivo abrogation of IL-1 signaling reduces Th17 levels in IL- -/- mice. Similar to IL-/- mice, Crohn's disease patients have elevated numbers of Th17 cells, and ex vivo production of IL-17 by these cells is inhibited upon anti-IL-1R treatment. Stimulated DCs from Crohn's patients produce high levels of IL-1. In intestinal mucosa, IL-10 levels were inversely proportional to those of IL-1 and IL-17, suggesting a similar mechanism of control of Th17 cells in human pathology. IL-10 thus constrains Th17 cell development through repression of IL-1, and in turn tempers autoimmune responses.
520 $a Taken together, our data expands upon the known IL-10 biology in immune regulation of antitumor immunity and autoimmunity.
590 $a School code: 0127.
650 4 $a Biology, Molecular. $3 226919
650 4 $a Biology, Cell. $3 226967
650 4 $a Health Sciences, Immunology. $3 226966
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710 2 $a University of Michigan. $3 212464
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