The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice
Open accessAbstract
Stat3 plays an essential role in IL-10 signaling pathways. A myeloid cell-specific deletion of Stat3 resulted in inflammatory cytokine production and development of chronic enterocolitis with enhanced Th1 responses in mice. In this study, we analyzed the mechanism by which a Stat3 deficiency in myeloid cells led to the induction of chronic enterocolitis in vivo. Even in the absence of Stat1, which is essential for IFN-gamma signaling pathways, Stat3 mutant mice developed chronic enterocolitis. TNF-alpha/Stat3 double-mutant mice developed severe chronic enterocolitis with enhanced Th1 cell development. IL-12p40/Stat3 double-mutant mice, however, showed normal Th1 responses and no inflammatory change in the colon. RAG2/Stat3 double-mutant mice did not develop enterocolitis, either. These findings indicate that overproduction of IL-12p40, which induces potent Th1 responses, is essential for the development of chronic enterocolitis in Stat3 mutant mice. Furthermore, enterocolitis was significantly improved and IFN-gamma production by T cells was reduced in TLR4/Stat3 double-mutant mice, indicating that TLR4-mediated recognition of microbial components triggers aberrant IL-12p40 production by myeloid cells, leading to the development of enterocolitis. Thus, this study clearly established a sequential innate and acquired immune mechanism for the development of Th1-dependent enterocolitis.
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Cites
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A Toll-like receptor recognizes bacterial DNA
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“TLR9, which induces potent Th1 responses through recognition of CpG DNA in vivo, is one such candidate (50).”
BackgroundSelf-citationToll-like receptors: critical proteins linking innate and acquired immunity
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Cited by
Toll-like receptors in innate immunity
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Self-citationRole of the gut microbiota in immunity and inflammatory disease
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The immunological and genetic basis of inflammatory bowel disease
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Metadata
- Authors
- Kobayashi, M., Kweon, M.-N., Kuwata, H., Schreiber, R. D., Kiyono, H., Takeda, K., & Akira, S.
- Venue
- Journal of Clinical Investigation
- Published
- 2003-05-01
- Volume
- 111
- Issue
- 9
- Pages
- 1297-1308
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1975421800
- Cited by
- 251
- References
- 10
- FWCI
- 9.27
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Kobayashi, M., Kweon, M.-N., Kuwata, H., Schreiber, R. D., Kiyono, H., Takeda, K., & Akira, S. (2003). Toll-like receptor-dependent production of IL-12p40 causes chronic enterocolitis in myeloid cell-specific Stat3-deficient mice. Journal of Clinical Investigation. https://doi.org/10.1172/jci17085
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