Regulation of Cytokine Secretion in Human CD127(+) LTi-like Innate Lymphoid Cells by Toll-like Receptor 2
ABSTRACT Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express IL-2, IL-5, and IL-13 after activation with physiologic stimuli such as common γ-chain cytokines, Toll-like receptor (TLR) 2 ligands, or IL-23. Whereas TLR2 signaling induced IL-5, IL-13, and IL-22 expression in a nuclear factor κB (NF-κB)-dependent manner, IL-23 costimulation induced only IL-22 production. CD127(+) LTi-like ILC displayed clonal heterogeneity for IL-13 and IL-5 production, suggesting in vivo polarization. Finally, we identified a role for autocrine IL-2 signaling in mediating the effects of TLR2 stimulation on CD56(+)CD127(+) and CD127(+) LTi-like ILC. These results indicate that human LTi-like ILC can directly sense bacterial components and unravel a previously unrecognized functional heterogeneity among this important population of innate lymphoid cells.
- SourceAvailable from: Tobias M Hohl
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- "IL-6, IL-1b, and IL-23 produced by antigen-presenting cells regulate IL-22 expression in innate cells. It has also been suggested that direct stimulation of TLRs on innate immune cells can induce IL-22 expression (Crellin et al., 2010; Martin et al., 2009; Sutton et al., 2009). Although Th17 cells and gd T cells that express the transcription factors RORgt and the aryl hydrocarbon receptor (AHR) can produce IL-22, the primary source for flagellin-mediated IL-22 expression in the intestine is CD3 3 À CD127 + innate lymphoid cells (ILC) (Van Maele et al., 2010). "
ABSTRACT: Microbial penetration of the intestinal epithelial barrier triggers inflammatory responses that include induction of the bactericidal C-type lectin RegIIIγ. Systemic administration of flagellin, a bacterial protein that stimulates Toll-like receptor 5 (TLR5), induces epithelial expression of RegIIIγ and protects mice from intestinal colonization with antibiotic-resistant bacteria. Flagellin-induced RegIIIγ expression is IL-22 dependent, but how TLR signaling leads to IL-22 expression is incompletely defined. By using conditional depletion of lamina propria dendritic cell (LPDC) subsets, we demonstrated that CD103(+)CD11b(+) LPDCs, but not monocyte-derived CD103(-)CD11b(+) LPDCs, expressed high amounts of IL-23 after bacterial flagellin administration and drove IL-22-dependent RegIIIγ production. Maximal expression of IL-23 subunits IL-23p19 and IL-12p40 occurred within 60 min of exposure to flagellin. IL-23 subsequently induced a burst of IL-22 followed by sustained RegIIIγ expression. Thus, CD103(+)CD11b(+) LPDCs, in addition to promoting long-term tolerance to ingested antigens, also rapidly produce IL-23 in response to detection of flagellin in the lamina propria.Immunity 02/2012; 36(2):276-87. DOI:10.1016/j.immuni.2011.12.011 · 19.75 Impact Factor
Conference Paper: Natural language understanding based on background knowledge[Show abstract] [Hide abstract]
ABSTRACT: Natural language understanding can be divided into five hierarchical levels, each level related to other levels. Background knowledge consists of all level's units and their usage in the real language environment. Co-occurence information of any two units of the same level can be provided by background knowledge. This paper discusses the usage of background knowledge in automatic Chinese word segmentation, and text understanding based on semantic relationshipsTENCON '93. Proceedings. Computer, Communication, Control and Power Engineering.1993 IEEE Region 10 Conference on; 11/1993
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ABSTRACT: Research has identified what can be considered a family of innate lymphoid cells (ILCs) that includes not only natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells but also cells that produce interleukin 5 (IL-5), IL-13, IL-17 and/or IL-22. These ILC subsets are developmentally related, requiring expression of the transcriptional repressor Id2 and cytokine signals through the common γ-chain of the IL-2 receptor. The functional differentiation of ILC subsets is orchestrated by distinct transcription factors. Analogous to helper T cell subsets, these evolutionarily conserved yet distinct ILCs seem to have important roles in protective immunity, and their dysregulation can promote immune pathology.Nature Immunology 01/2011; 12(1):21-7. DOI:10.1038/ni.1962 · 24.97 Impact Factor