Stat6 dependent goblet cell hyperplasia during intestinal nematode infection.
To identify the role of signal transducer and activator of transcription factor 6 (Stat6) in the development of intestinal goblet cell hyperplasia during nematode infection, we compared the number of goblet cells in Stat6 deficient (Stat6 -/-) mice with that generated in wild-type (Stat6 +/+) mice in Trichinella spiralis infection. The number of goblet cells significantly increased with infection in wild-type mice. However, Stat6 -/- failed to generate infection-induced goblet cell hyperplasia and a significantly lower number of goblet cells was observed in Stat6 -/- mice on days 14 and 21 postinfection compared to Stat6 +/+ mice. In addition to suppressed goblet cell numbers, Stat6 -/- mice exhibited severe impairment in their ability to produce IL-4 and IL-13 and to expel the parasites from the gut. Our study clearly shows an essential role of Stat6 in intestinal goblet cell hyperplasia which accompanies this infection. We postulate that Th2 cytokines regulate the development of goblet cell hyperplasia in gut during nematode infection via Stat6 activation and that the increased number of goblet cells plays an important role in host protective immunity against the infection.
Khan
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Intestinal Disease Research Program, McMaster University, Hamilton, Ontario, Canada.
Blennerhasset
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Ma
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Matthaei
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Collins
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SM
D000818:Animals; D020397:Goblet Cells / Q000276:immunology / Q000473:pathology*; D007411:Intestinal Diseases, Parasitic / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017160:Trichinella spiralis / Q000276:immunology* / Q000302:isolation & purification; D014235:Trichinellosis / Q000276:immunology* / Q000469:parasitology
D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators