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Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in Salmonella infection.

Chen VL, Surana NK, Duan J, Kasper DL - PLoS ONE (2013)

Bottom Line: These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling.LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium.Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
Interleukin (IL)-1 signaling plays a critical role in intestinal immunology. Here, we report that the major population of intestinal lamina propria lymphocytes expressing IL-1 receptor 1 (IL-1R1) is the lymphoid tissue inducer (LTi)-like cell, a type of innate lymphoid cell. These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling. LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium. Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota. LTi-like cells require IL-1R1 for production of protective cytokines and confer protection in infectious colitis, and their cell numbers in the colon depend upon having a microbiome.

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IL-1R1 is required for IL-23-stimulated IL-17 and IL-22 production by LTi-like cells in vitro.(A and B) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IL-22 (A) or IL-17 (B). (C) Box and whiskers plot depicting percent of colonic LTi-like cells isolated from Rag1−/− (R) C57BL/6J mice that produce IL-22. (D) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IFN-γ. Except in (C), cells were isolated from WT (top panels) or IL-1R1−/− C57BL/6J mice (bottom panels). Cells were stimulated by rIL-23 (23; right panels) or medium (M; left panels). Box and whisker plots representative of at least three independent experiments. *, p<0.05; NS, not significant. For box and whisker plots, line represents median, box represents 25th to 75th percentile range, and whiskers represent range.
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pone-0065405-g003: IL-1R1 is required for IL-23-stimulated IL-17 and IL-22 production by LTi-like cells in vitro.(A and B) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IL-22 (A) or IL-17 (B). (C) Box and whiskers plot depicting percent of colonic LTi-like cells isolated from Rag1−/− (R) C57BL/6J mice that produce IL-22. (D) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IFN-γ. Except in (C), cells were isolated from WT (top panels) or IL-1R1−/− C57BL/6J mice (bottom panels). Cells were stimulated by rIL-23 (23; right panels) or medium (M; left panels). Box and whisker plots representative of at least three independent experiments. *, p<0.05; NS, not significant. For box and whisker plots, line represents median, box represents 25th to 75th percentile range, and whiskers represent range.

Mentions: Having demonstrated that cLP LTi-like cells are major innate IL-22 producers and that virtually all are IL-1R1+, we were interested in whether IL-1R1 signaling is important for LTi-like cell production of Th17 cytokines, as it is in other cell populations [41], [42], [43], [48]. After culturing small-intestinal and cLP cell suspensions (which include LTi-like cells, among other cell types) isolated from WT or IL-1R1−/− mice with either medium alone (control) or IL-23, a known positive regulator of IL-17 [41] and IL-22 [38], [41], we measured the proportion of LTi-like cells that produced IL-22 and IL-17. As expected, IL-23-stimulated WT cLP LTi-like cells produced IL-22 in greater proportions than did unstimulated cells (Fig. 3A). However, IL-23 did not stimulate IL-1R1−/− cLP LTi-like cells to produce IL-22 in greater proportions than media alone (Fig. 3A). Of note, unstimulated WT and IL-1R1−/− cLP LTi-like cells produced IL-22 in comparable proportions (Fig. 3A). Qualitatively, these findings were similar with IL-17, with IL-1R1 being required for IL-23 stimulation of IL-17 as well; however, a smaller proportion of LTi-like cells produced IL-17 than IL-22 (Fig. 3B). Again, the percentages of WT and IL-1R1−/− LTi-like cells producing IL-17 are similar at baseline (Fig. 3B). The pattern of small-intestinal LTi-like cell production of IL-22 and IL-17 in WT and IL-1R1−/− mice was qualitatively similar to that of colonic LTi-like cells, in that IL-23 stimulation increased production of IL-22 and IL-17 in WT but not IL-1R1−/− LTi-like cells (data not shown). Colonic LTi-like cells from Rag1−/− mice also increased IL-22 production after IL-23 stimulation (Fig. 3C). Neither WT nor IL-1R1−/− LTi-like cells produce IFN-γ either at baseline or following stimulation with IL-23 (Fig. 3D), which demonstrates that cytokine stimulation by IL-23 is not nonspecific. Taken together, these data indicate that intestinal LTi-like cells require IL-1R1 for IL-23 stimulation of IL-22 and IL-17 but that IL-1R1 is not involved in homeostatic control of either of these cytokines.


Role of murine intestinal interleukin-1 receptor 1-expressing lymphoid tissue inducer-like cells in Salmonella infection.

Chen VL, Surana NK, Duan J, Kasper DL - PLoS ONE (2013)

IL-1R1 is required for IL-23-stimulated IL-17 and IL-22 production by LTi-like cells in vitro.(A and B) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IL-22 (A) or IL-17 (B). (C) Box and whiskers plot depicting percent of colonic LTi-like cells isolated from Rag1−/− (R) C57BL/6J mice that produce IL-22. (D) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IFN-γ. Except in (C), cells were isolated from WT (top panels) or IL-1R1−/− C57BL/6J mice (bottom panels). Cells were stimulated by rIL-23 (23; right panels) or medium (M; left panels). Box and whisker plots representative of at least three independent experiments. *, p<0.05; NS, not significant. For box and whisker plots, line represents median, box represents 25th to 75th percentile range, and whiskers represent range.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3672157&req=5

pone-0065405-g003: IL-1R1 is required for IL-23-stimulated IL-17 and IL-22 production by LTi-like cells in vitro.(A and B) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IL-22 (A) or IL-17 (B). (C) Box and whiskers plot depicting percent of colonic LTi-like cells isolated from Rag1−/− (R) C57BL/6J mice that produce IL-22. (D) Box and whiskers plot depicting percent of WT (W) or IL-1R1−/− (I) colonic CD4+ LTi-like cells that produce IFN-γ. Except in (C), cells were isolated from WT (top panels) or IL-1R1−/− C57BL/6J mice (bottom panels). Cells were stimulated by rIL-23 (23; right panels) or medium (M; left panels). Box and whisker plots representative of at least three independent experiments. *, p<0.05; NS, not significant. For box and whisker plots, line represents median, box represents 25th to 75th percentile range, and whiskers represent range.
Mentions: Having demonstrated that cLP LTi-like cells are major innate IL-22 producers and that virtually all are IL-1R1+, we were interested in whether IL-1R1 signaling is important for LTi-like cell production of Th17 cytokines, as it is in other cell populations [41], [42], [43], [48]. After culturing small-intestinal and cLP cell suspensions (which include LTi-like cells, among other cell types) isolated from WT or IL-1R1−/− mice with either medium alone (control) or IL-23, a known positive regulator of IL-17 [41] and IL-22 [38], [41], we measured the proportion of LTi-like cells that produced IL-22 and IL-17. As expected, IL-23-stimulated WT cLP LTi-like cells produced IL-22 in greater proportions than did unstimulated cells (Fig. 3A). However, IL-23 did not stimulate IL-1R1−/− cLP LTi-like cells to produce IL-22 in greater proportions than media alone (Fig. 3A). Of note, unstimulated WT and IL-1R1−/− cLP LTi-like cells produced IL-22 in comparable proportions (Fig. 3A). Qualitatively, these findings were similar with IL-17, with IL-1R1 being required for IL-23 stimulation of IL-17 as well; however, a smaller proportion of LTi-like cells produced IL-17 than IL-22 (Fig. 3B). Again, the percentages of WT and IL-1R1−/− LTi-like cells producing IL-17 are similar at baseline (Fig. 3B). The pattern of small-intestinal LTi-like cell production of IL-22 and IL-17 in WT and IL-1R1−/− mice was qualitatively similar to that of colonic LTi-like cells, in that IL-23 stimulation increased production of IL-22 and IL-17 in WT but not IL-1R1−/− LTi-like cells (data not shown). Colonic LTi-like cells from Rag1−/− mice also increased IL-22 production after IL-23 stimulation (Fig. 3C). Neither WT nor IL-1R1−/− LTi-like cells produce IFN-γ either at baseline or following stimulation with IL-23 (Fig. 3D), which demonstrates that cytokine stimulation by IL-23 is not nonspecific. Taken together, these data indicate that intestinal LTi-like cells require IL-1R1 for IL-23 stimulation of IL-22 and IL-17 but that IL-1R1 is not involved in homeostatic control of either of these cytokines.

Bottom Line: These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling.LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium.Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.

ABSTRACT
Interleukin (IL)-1 signaling plays a critical role in intestinal immunology. Here, we report that the major population of intestinal lamina propria lymphocytes expressing IL-1 receptor 1 (IL-1R1) is the lymphoid tissue inducer (LTi)-like cell, a type of innate lymphoid cell. These cells are significant producers of IL-22, and this IL-22 production depends on IL-1R1 signaling. LTi-like cells are required for defense against Salmonella enterica serovar Typhimurium. Moreover, colonic LTi-like cell numbers depend on the presence of the intestinal microbiota. LTi-like cells require IL-1R1 for production of protective cytokines and confer protection in infectious colitis, and their cell numbers in the colon depend upon having a microbiome.

Show MeSH
Related in: MedlinePlus