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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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Reprogramming of TH17 profiles to TFH phenotype in the Peyer’s patchesa) Flow cytometry of CD4+ CD44high eYFP− T cells (left panel), CD4+ eYFP+ cells (middle panel) and eYFP+ γδ T cells (right panel) showing expression of CXCR5 and PD-1 in LN (upper row) or PP (lower row) of Il17aCreR26ReYFP mice. Mean values +/− SD of CXCR5+ PD-1high cells are given in histograms. b) Flow cytometry of CD4+ eYFP+ T cells (upper panel) and CD4+ eYFP+ T cells expressing CXCR5 and PD-1 (lower panel) in LN, PP, and LP of Tcra−/− mice transferred with eYFP+ TH17 cells and analysed three months after transfer. Mean values of CXCR5+ PD-1high eYFP+ cells +/− SD are shown in histograms. c) Proportion of CXCR5+ PD-1high eYFP− CD44high CD4+ or eYFP+ CD4+ T cells in draining LN or spinal cord of Il17aCreR26ReYFP mice 20d after immunization with MOG+CFA. d) Quantitative PCR analysis for expression of indicated mRNA in FACS purified CXCR5+ eYFP+ (PP eYFP+ TFH), CXCR5− eYFP+ (LN TH17), CXCR5+ eYFP− (PP TFH) and naïve CD4+ T cells from Il17aCreR26ReYFP mice. mRNA expression is relative to Hprt. Data are representative of at least three independent experiments.
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Figure 2: Reprogramming of TH17 profiles to TFH phenotype in the Peyer’s patchesa) Flow cytometry of CD4+ CD44high eYFP− T cells (left panel), CD4+ eYFP+ cells (middle panel) and eYFP+ γδ T cells (right panel) showing expression of CXCR5 and PD-1 in LN (upper row) or PP (lower row) of Il17aCreR26ReYFP mice. Mean values +/− SD of CXCR5+ PD-1high cells are given in histograms. b) Flow cytometry of CD4+ eYFP+ T cells (upper panel) and CD4+ eYFP+ T cells expressing CXCR5 and PD-1 (lower panel) in LN, PP, and LP of Tcra−/− mice transferred with eYFP+ TH17 cells and analysed three months after transfer. Mean values of CXCR5+ PD-1high eYFP+ cells +/− SD are shown in histograms. c) Proportion of CXCR5+ PD-1high eYFP− CD44high CD4+ or eYFP+ CD4+ T cells in draining LN or spinal cord of Il17aCreR26ReYFP mice 20d after immunization with MOG+CFA. d) Quantitative PCR analysis for expression of indicated mRNA in FACS purified CXCR5+ eYFP+ (PP eYFP+ TFH), CXCR5− eYFP+ (LN TH17), CXCR5+ eYFP− (PP TFH) and naïve CD4+ T cells from Il17aCreR26ReYFP mice. mRNA expression is relative to Hprt. Data are representative of at least three independent experiments.

Mentions: The preferential accumulation of TH17 cells in PP prompted us to examine the possibility that they might play a role in helping germinal center B cell differentiation. T follicular helper (TFH) cells reside in germinal centers and play an essential role in germinal center B cells differentiation and their distinguishing features are the expression of CXCR5, PD-1, IL-21, ICOS and the transcription factor Bcl614-16. We determined that about ~13-20% of eYFP+ TH17 cells as well as a similar proportion of eYFP− cells present in the PP of non-immune Il17aCreR26ReYFP mice expressed CXCR5 and PD-1, whereas PP eYFP+ γδ T cells did not express these TFH markers (Fig. 2a).


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)

Reprogramming of TH17 profiles to TFH phenotype in the Peyer’s patchesa) Flow cytometry of CD4+ CD44high eYFP− T cells (left panel), CD4+ eYFP+ cells (middle panel) and eYFP+ γδ T cells (right panel) showing expression of CXCR5 and PD-1 in LN (upper row) or PP (lower row) of Il17aCreR26ReYFP mice. Mean values +/− SD of CXCR5+ PD-1high cells are given in histograms. b) Flow cytometry of CD4+ eYFP+ T cells (upper panel) and CD4+ eYFP+ T cells expressing CXCR5 and PD-1 (lower panel) in LN, PP, and LP of Tcra−/− mice transferred with eYFP+ TH17 cells and analysed three months after transfer. Mean values of CXCR5+ PD-1high eYFP+ cells +/− SD are shown in histograms. c) Proportion of CXCR5+ PD-1high eYFP− CD44high CD4+ or eYFP+ CD4+ T cells in draining LN or spinal cord of Il17aCreR26ReYFP mice 20d after immunization with MOG+CFA. d) Quantitative PCR analysis for expression of indicated mRNA in FACS purified CXCR5+ eYFP+ (PP eYFP+ TFH), CXCR5− eYFP+ (LN TH17), CXCR5+ eYFP− (PP TFH) and naïve CD4+ T cells from Il17aCreR26ReYFP mice. mRNA expression is relative to Hprt. Data are representative of at least three independent experiments.
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Figure 2: Reprogramming of TH17 profiles to TFH phenotype in the Peyer’s patchesa) Flow cytometry of CD4+ CD44high eYFP− T cells (left panel), CD4+ eYFP+ cells (middle panel) and eYFP+ γδ T cells (right panel) showing expression of CXCR5 and PD-1 in LN (upper row) or PP (lower row) of Il17aCreR26ReYFP mice. Mean values +/− SD of CXCR5+ PD-1high cells are given in histograms. b) Flow cytometry of CD4+ eYFP+ T cells (upper panel) and CD4+ eYFP+ T cells expressing CXCR5 and PD-1 (lower panel) in LN, PP, and LP of Tcra−/− mice transferred with eYFP+ TH17 cells and analysed three months after transfer. Mean values of CXCR5+ PD-1high eYFP+ cells +/− SD are shown in histograms. c) Proportion of CXCR5+ PD-1high eYFP− CD44high CD4+ or eYFP+ CD4+ T cells in draining LN or spinal cord of Il17aCreR26ReYFP mice 20d after immunization with MOG+CFA. d) Quantitative PCR analysis for expression of indicated mRNA in FACS purified CXCR5+ eYFP+ (PP eYFP+ TFH), CXCR5− eYFP+ (LN TH17), CXCR5+ eYFP− (PP TFH) and naïve CD4+ T cells from Il17aCreR26ReYFP mice. mRNA expression is relative to Hprt. Data are representative of at least three independent experiments.
Mentions: The preferential accumulation of TH17 cells in PP prompted us to examine the possibility that they might play a role in helping germinal center B cell differentiation. T follicular helper (TFH) cells reside in germinal centers and play an essential role in germinal center B cells differentiation and their distinguishing features are the expression of CXCR5, PD-1, IL-21, ICOS and the transcription factor Bcl614-16. We determined that about ~13-20% of eYFP+ TH17 cells as well as a similar proportion of eYFP− cells present in the PP of non-immune Il17aCreR26ReYFP mice expressed CXCR5 and PD-1, whereas PP eYFP+ γδ T cells did not express these TFH markers (Fig. 2a).

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