Dependence of IL-4, IL-13, and Nematode-Induced Alterations in Murine Small Intestinal Smooth Muscle Contractility on Stat6 and Enteric Nerves

Zhao, Aiping; McDermott, Joseph; Urban, Joseph F.; Gause, William C.; Madden, Kathleen B.; Yeung, Karla Au; Morris, Suzanne C.; Finkelman, Fred D.; Shea‐Donohue, Terez

doi:10.4049/jimmunol.171.2.948

Cited by 174 publications

(256 citation statements)

References 26 publications

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“…IL-25 is a potent inductor for the production of IL-4, IL-5, and IL-13 (8). These Th2 cytokines, particularly IL-4 and IL-13, previously have been reported to cause a number of changes in intestinal epithelial functions, such as balance of ion, mucosal fluids absorption (15), and increase in intestinal smooth muscle contraction (16). IL-13 was found primarily to mediate massive histological changes in the gastrointestinal mucosa of mice treated with rIL-25 (8).…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

et al. 2008

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“…Other cell types of the lung and intestine can also respond to IL-13. Both IL-4 and IL-13 can be detected in intestinal smooth muscle during nematode infection (40) and are required, with STAT-6, to induce muscle contractility, a putative host mechanism for parasite expulsion (40,41). Likewise, airway smooth muscle can produce IL-13 and has been linked to an autocrine pathway inducing smooth muscle hypertrophy, a feature of asthma pathophysiology (42).…”

Section: Discussionmentioning

confidence: 99%

Intraepithelial NK Cell-Derived IL-13 Induces Intestinal Pathology Associated with Nematode Infection

McDermott

Humphreys

Forman

et al. 2005

The Journal of Immunology

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IL-13 is a Th2-derived cytokine associated with pathological changes in asthma and ulcerative colitis. Moreover, it plays a major role in the control of gut nematode infection and associated immunopathology. The current paradigm is that these effects are due to T cell-derived IL-13. We show in this study that an innate source of IL-13, the intraepithelial NK cell, is responsible for the disruption of intestinal tissue architecture and induction of goblet cell hyperplasia that characterizes infection with the intestinal helminth Trichinella spiralis. IL-13 or IL-4Rα (but not IL-4) null mice failed to induce intestinal pathology. Unexpectedly, SCID and athymic mice developed the same pathology found in immunocompetent mice following infection. Moreover, immunodeficient mice expressed IL-13 in the intestine, and abnormal mucosal pathology was reduced by in vivo administration of a soluble IL-13 antagonist. IL-13 expression was induced in non-T intraepithelial CD3− NK cells. Epithelial cells expressed the IL-13 signaling receptor, IL-13Rα1, and after infection, IL-4Rα. Furthermore, the soluble IL-13 decoy receptor IL-13Rα2, which regulates IL-13 responses, was also induced upon infection. These data provide the first evidence that intestinal tissue restructuring during helminth infection is an innate event dependent on IL-13 production by NK cells resident in the epithelium of the intestine.

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“…An inflammatory cell infiltrate develops around the invading parasitic larvae, resulting in a border of cells that delineate a loosely defined, cyst-like structure (5,6). Although the mechanism of worm expulsion remains uncertain, direct effects of IL-4 and IL-13 on gut tissue are probably important (7)(8)(9), and some studies have suggested that an effective memory response is also associated with delayed larval development before emergence into the lumen (5,10). The CD4 T cell response has not been examined at peripheral sites of infection, but pronounced increases in CD4 T cell IL-4 and IL-13, but not IFN-␥, are detected in the mesenteric lymph node (MLN) as early as day 8 after primary inoculation and secondary challenge (11,12).…”

mentioning

confidence: 99%

Peripheral CD4 T Cells Rapidly Accumulate at the Host:Parasite Interface during an Inflammatory Th2 Memory Response

Morimoto

Whitmire

et al. 2004

The Journal of Immunology

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Memory peripheral Th2 immune responses to infectious pathogens are not well studied due to the lack of suitable models and the difficulty of assessing Th2 cytokine expression at sites of inflammation. We have examined the localized immune response to a nematode parasite that encysts in the small intestine. An unexpected architecture was observed on day 4 of the memory response, with granulocytes and macrophages infiltrating the cyst and CD4+, TCR-αβ+ T cells surrounding the cyst. Laser capture microdissection analysis showed a pronounced CD4-dependent Th2 cytokine pattern at the cyst region only during the memory response, demonstrating that the Th2 memory response is readily distinguished from the primary response by the rapid accumulation of Th2 effector cells at the host:parasite interface.

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Dependence of IL-4, IL-13, and Nematode-Induced Alterations in Murine Small Intestinal Smooth Muscle Contractility on Stat6 and Enteric Nerves

Cited by 174 publications

References 26 publications

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

Inhibitory Effect of Recombinant IL-25 on the Development of Dextran Sulfate Sodium-Induced Experimental Colitis in Mice

Intraepithelial NK Cell-Derived IL-13 Induces Intestinal Pathology Associated with Nematode Infection

Peripheral CD4 T Cells Rapidly Accumulate at the Host:Parasite Interface during an Inflammatory Th2 Memory Response

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