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Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses.

Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J, Steinmetz OM, Stockinger B - Nat. Immunol. (2013)

Bottom Line: Intestinal Peyer's patches are essential lymphoid organs for the generation of T cell-dependent immunoglobulin A (IgA) for gut homeostasis.Through the use of interleukin 17 (IL-17) fate-reporter mice, we found here that endogenous cells of the TH17 subset of helper T cells in lymphoid organs of naive mice 'preferentially' homed to the intestines and were maintained independently of IL-23.In Peyer's patches, such TH17 cells acquired a follicular helper T cell (TFH cell) phenotype and induced the development of IgA-producing germinal center B cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.

ABSTRACT
Intestinal Peyer's patches are essential lymphoid organs for the generation of T cell-dependent immunoglobulin A (IgA) for gut homeostasis. Through the use of interleukin 17 (IL-17) fate-reporter mice, we found here that endogenous cells of the TH17 subset of helper T cells in lymphoid organs of naive mice 'preferentially' homed to the intestines and were maintained independently of IL-23. In Peyer's patches, such TH17 cells acquired a follicular helper T cell (TFH cell) phenotype and induced the development of IgA-producing germinal center B cells. Mice deficient in TH17 cells failed to generate antigen-specific IgA responses, which provides evidence that TH17 cells are the crucial subset required for the production of high-affinity T cell-dependent IgA.

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IL-23 is dispensable for homeostatic maintenance and plasticity of intestinal TH17a) Number of eYFP+ TH17 cells in LN and PP of Il17aCreR26ReYFP (B6, closed dots) and Il17aCreR26ReYFPIl23a-deficient (Il23a−/−, open dots) mice. b) Flow cytometry of eYFP+ CD4+ T cells showing expression of CXCR5 and PD-1 in PP of B6 and Il23a−/− mice. c) Quantitative PCR analysis for expression of indicated mRNA in FACS purified PP or LN eYFP+ CD4+ T cells from B6 and Il23a−/− mice. d) Flow cytometry of eYFP+ CD4+ T cells from LN or PP of B6 and Il23a−/− mice showing intracellular staining for IL-17, IFNγ and IL-22. Data are representative of at least three independent experiments. *, p-value < 0.01.
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Figure 3: IL-23 is dispensable for homeostatic maintenance and plasticity of intestinal TH17a) Number of eYFP+ TH17 cells in LN and PP of Il17aCreR26ReYFP (B6, closed dots) and Il17aCreR26ReYFPIl23a-deficient (Il23a−/−, open dots) mice. b) Flow cytometry of eYFP+ CD4+ T cells showing expression of CXCR5 and PD-1 in PP of B6 and Il23a−/− mice. c) Quantitative PCR analysis for expression of indicated mRNA in FACS purified PP or LN eYFP+ CD4+ T cells from B6 and Il23a−/− mice. d) Flow cytometry of eYFP+ CD4+ T cells from LN or PP of B6 and Il23a−/− mice showing intracellular staining for IL-17, IFNγ and IL-22. Data are representative of at least three independent experiments. *, p-value < 0.01.

Mentions: TH17 cell plasticity in autoimmune settings is strongly dependent on IL-2312. In order to test whether IL-23 is similarly involved in plasticity of intestinal TH17 cells towards TFH, we analysed Il17aCreR26ReYFP mice crossed onto a p19 (Il23a)-deficient background. Firstly, and in contrast to the well-defined role of IL-23 in TH17 maintenance in autoimmune settings, IL-23 was dispensable for the survival of intestinal TH17 cells, as similar numbers of TH17 cells were present in LN and PP of Il23a-deficient and wild-type Il17aCreR26ReYFP mice (Fig.3a). Furthermore, phenotypic conversion to a TFH phenotype occurred to the same extent in IL-23-deficient and wild-type Il17aCreR26ReYFP mice (Fig.3b) and TH17 cells with the TFH phenotype in Il23a−/− reporter mice upregulated Bcl6 and Il21 expression similar to TH17 cells from wild-type reporter mice (Fig.3c). In contrast, in accordance with previous observations12, TH17 cells were unable to deviate towards IFN-γ expression and did not express IL-22 in Il23a-deficient mice (Fig.3d). These data indicate that the intestinal, steady-state population of TH17 cells has distinct features from the TH17 cells elicited by immunization in the periphery.


Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses.

Hirota K, Turner JE, Villa M, Duarte JH, Demengeot J, Steinmetz OM, Stockinger B - Nat. Immunol. (2013)

IL-23 is dispensable for homeostatic maintenance and plasticity of intestinal TH17a) Number of eYFP+ TH17 cells in LN and PP of Il17aCreR26ReYFP (B6, closed dots) and Il17aCreR26ReYFPIl23a-deficient (Il23a−/−, open dots) mice. b) Flow cytometry of eYFP+ CD4+ T cells showing expression of CXCR5 and PD-1 in PP of B6 and Il23a−/− mice. c) Quantitative PCR analysis for expression of indicated mRNA in FACS purified PP or LN eYFP+ CD4+ T cells from B6 and Il23a−/− mice. d) Flow cytometry of eYFP+ CD4+ T cells from LN or PP of B6 and Il23a−/− mice showing intracellular staining for IL-17, IFNγ and IL-22. Data are representative of at least three independent experiments. *, p-value < 0.01.
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Related In: Results  -  Collection

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Figure 3: IL-23 is dispensable for homeostatic maintenance and plasticity of intestinal TH17a) Number of eYFP+ TH17 cells in LN and PP of Il17aCreR26ReYFP (B6, closed dots) and Il17aCreR26ReYFPIl23a-deficient (Il23a−/−, open dots) mice. b) Flow cytometry of eYFP+ CD4+ T cells showing expression of CXCR5 and PD-1 in PP of B6 and Il23a−/− mice. c) Quantitative PCR analysis for expression of indicated mRNA in FACS purified PP or LN eYFP+ CD4+ T cells from B6 and Il23a−/− mice. d) Flow cytometry of eYFP+ CD4+ T cells from LN or PP of B6 and Il23a−/− mice showing intracellular staining for IL-17, IFNγ and IL-22. Data are representative of at least three independent experiments. *, p-value < 0.01.
Mentions: TH17 cell plasticity in autoimmune settings is strongly dependent on IL-2312. In order to test whether IL-23 is similarly involved in plasticity of intestinal TH17 cells towards TFH, we analysed Il17aCreR26ReYFP mice crossed onto a p19 (Il23a)-deficient background. Firstly, and in contrast to the well-defined role of IL-23 in TH17 maintenance in autoimmune settings, IL-23 was dispensable for the survival of intestinal TH17 cells, as similar numbers of TH17 cells were present in LN and PP of Il23a-deficient and wild-type Il17aCreR26ReYFP mice (Fig.3a). Furthermore, phenotypic conversion to a TFH phenotype occurred to the same extent in IL-23-deficient and wild-type Il17aCreR26ReYFP mice (Fig.3b) and TH17 cells with the TFH phenotype in Il23a−/− reporter mice upregulated Bcl6 and Il21 expression similar to TH17 cells from wild-type reporter mice (Fig.3c). In contrast, in accordance with previous observations12, TH17 cells were unable to deviate towards IFN-γ expression and did not express IL-22 in Il23a-deficient mice (Fig.3d). These data indicate that the intestinal, steady-state population of TH17 cells has distinct features from the TH17 cells elicited by immunization in the periphery.

Bottom Line: Intestinal Peyer's patches are essential lymphoid organs for the generation of T cell-dependent immunoglobulin A (IgA) for gut homeostasis.Through the use of interleukin 17 (IL-17) fate-reporter mice, we found here that endogenous cells of the TH17 subset of helper T cells in lymphoid organs of naive mice 'preferentially' homed to the intestines and were maintained independently of IL-23.In Peyer's patches, such TH17 cells acquired a follicular helper T cell (TFH cell) phenotype and induced the development of IgA-producing germinal center B cells.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK.

ABSTRACT
Intestinal Peyer's patches are essential lymphoid organs for the generation of T cell-dependent immunoglobulin A (IgA) for gut homeostasis. Through the use of interleukin 17 (IL-17) fate-reporter mice, we found here that endogenous cells of the TH17 subset of helper T cells in lymphoid organs of naive mice 'preferentially' homed to the intestines and were maintained independently of IL-23. In Peyer's patches, such TH17 cells acquired a follicular helper T cell (TFH cell) phenotype and induced the development of IgA-producing germinal center B cells. Mice deficient in TH17 cells failed to generate antigen-specific IgA responses, which provides evidence that TH17 cells are the crucial subset required for the production of high-affinity T cell-dependent IgA.

Show MeSH
Related in: MedlinePlus