scholarly journals Myelin-specific T helper 17 cells promote adult hippocampal neurogenesis through indirect mechanisms

F1000Research ◽  
2017 ◽  
Vol 3 ◽  
pp. 169 ◽  
Author(s):  
Johannes Niebling ◽  
Annette E. Rünker ◽  
Sonja Schallenberg ◽  
Karsten Kretschmer ◽  
Gerd Kempermann
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Precursor Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Lymphoid Tissues ◽  
Base Line ◽  
T Helper ◽  
Th Cell

CD4+ T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear. Here, we explored the pro-proliferative potential of interleukin 17-producing T helper (Th17) cells, a developmentally and functionally distinct Th cell subset that is a key mediator of autoimmune neurodegeneration. We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors (TCR). In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche. Complementary studies in immunocompetent mice identified several receptors for Th17 cell-derived cytokines with mRNA expression in hippocampal precursor cells and dentate gyrus tissue, suggesting that Th17 cell activity in peripheral lymphoid tissues might promote hippocampal neurogenesis through secreted cytokines.

scholarly journals Myelin-specific T helper 17 cells promote adult hippocampal neurogenesis through indirect mechanisms

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 169 ◽  
Author(s):  
Johannes Niebling ◽  
Annette E. Rünker ◽  
Sonja Schallenberg ◽  
Karsten Kretschmer ◽  
Gerd Kempermann
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Precursor Cells ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Lymphoid Tissues ◽  
Base Line ◽  
T Helper ◽  
Th Cell

CD4+ T cells provide a neuro-immunological link in the regulation of adult hippocampal neurogenesis, but the exact mechanisms underlying enhanced neural precursor cell proliferation and the relative contribution of different T helper (Th) cell subsets have remained unclear. Here, we explored the proneurogenic potential of interleukin 17-producing T helper (Th17) cells, a developmentally and functionally distinct Th cell subset that is a key mediator of autoimmune neurodegeneration. We found that base-line proliferation of hippocampal precursor cells in a T cell-deficient mouse model of impaired hippocampal neurogenesis can be restored upon adoptive transfer with homogeneous Th17 populations enriched for myelin-reactive T cell receptors. In these experiments, enhanced proliferation was independent of direct interactions of infiltrating Th17 cells with precursor cells or neighboring cells in the hippocampal neurogenic niche. Complementary studies in immunocompetent mice identified several receptors for Th17 cell-derived cytokines with mRNA expression in hippocampal precursor cells and dentate gyrus tissue, suggesting that Th17 cell activity in peripheral lymphoid tissues might promote hippocampal neurogenesis through secreted cytokines.

scholarly journals CD4+T Cell Fate in Glomerulonephritis: A Tale of Th1, Th17, and Novel Treg Subtypes

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Christan F. Krebs ◽  
Oliver M. Steinmetz
Keyword(s):  
T Cell ◽  
Cell Fate ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Effector Cell ◽  
Renal Tissue ◽  
Cd4 T Cell ◽  
T Helper ◽  
Cell Lineages ◽  
High Degree

Multiple studies have identified CD4+T cells as central players of glomerulonephritis (GN). Cells of the Th1 and Th17 responses cause renal tissue damage, while Tregs mediate protection. Recently, a high degree of plasticity among these T cell lineages was proposed. During inflammation, Th17 cells were shown to have the potential of transdifferentiation into Th1, Th2, or alternatively anti-inflammatory Tr1 cells. Currently available data from studies in GN, however, do not indicate relevant Th17 to Th1 or Th2 conversion, leaving the Th17 cell fate enigmatic. Tregs, on the other hand, were speculated to transdifferentiate into Th17 cells. Again, data from GN do not support this concept. Rather, it seems that previously unrecognized subspecialized effector Treg lineages exist. These include Th1 specific Treg1 as well as Th17 directed Treg17 cells. Furthermore, a bifunctional Treg subpopulation was recently identified in GN, which secrets IL-17 and coexpresses Foxp3 together with the Th17 characteristic transcription factor RORγt. Similarities between these different and highly specialized effector Treg subpopulations with the corresponding T helper effector cell lineages might have resulted in previous misinterpretation as Treg transdifferentiation. In summary, Th17 cells have a relatively stable phenotype during GN, while, in the case of Tregs, currently available data suggest lineage heterogeneity rather than plasticity.

Evidence for Associations Between Th1/Th17 “Hybrid” Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy

2020 ◽  
Vol 105 (6) ◽  
pp. 1851-1867 ◽  
Author(s):  
Sijie Fang ◽  
Shuo Zhang ◽  
Yazhuo Huang ◽  
Yu Wu ◽  
Yi Lu ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
T Cell Subsets ◽  
Th1 Cell ◽  
Effector T Cell ◽  
Cell Lineages ◽  
Graves Orbitopathy ◽  
Ifn Γ

Abstract Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

Abstract MP50: Time Restricted Feeding Reduces Interleukin 17a Production Associated With Western Diets

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Gwendolyn K Davis ◽  
Daniel Fehrenbach ◽  
Charles D Smart ◽  
Claudia Edell ◽  
Jennifer Pollock ◽  
...  
Keyword(s):  
T Cell ◽  
Circadian Rhythms ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Fold Increase ◽  
Organ Damage ◽  
High Salt ◽  
Restricted Feeding ◽  
High Fat ◽  
Interleukin 17A

Circadian rhythms govern our daily physiological processes. However, disruption of circadian rhythms, as can occur with ad libitum Western diets, disrupt these processes leading to cardiometabolic diseases. Our lab and others have shown that Th17 cells, which produce interleukin 17A (IL-17A), are implicated in the development of cardiovascular and renal end-organ damage associated with high fat and/or high salt diets. Th17 cell differentiation and trafficking is regulated by the circadian clock and influenced by light-dark cycles. However, whether feeding-fasting rhythms influence Th17 cell responses is poorly understood. We tested the hypothesis that limiting food intake to the 12-hr active period (time-restricted feeding, TRF) mitigates high fat and high salt (HF/HS) diet induced T cell IL-17A production and target organ damage. Beginning at 8 weeks of age, male C57Bl/6J mice were placed on either a normal chow/normal salt (NC/NS) or a HF/HS diet for 20 weeks, with TRF intervention occurring during the last two weeks in the HF/HS + TRF group. Body weight was similarly significantly increased in the HF/HS and HF/HS + TRF groups in comparison to the NC/NS group. Th17 cells were significantly increased (2.6-fold increase, p = 0.02) in the Peyer’s patches (lymphoid aggregates found in the small intestines) of mice on HF/HS diet in comparison to those on NC/NS. Importantly, TRF abolished this increase. Renal CD4 + T cell IL-17A production, as measured by flow cytometry, was increased by HF/HS diet compared to NC/NS (3-fold increase, p = 0.02). Similarly, TRF abolished this increase. This study highlights how Western diets exacerbate intestinal and renal IL-17A production and the potential beneficial impact of a behavioral intervention, TRF, to mitigate the Th17 mediated inflammation associated with diet-induced obesity.

scholarly journals Pivotal Roles of T-Helper 17-Related Cytokines, IL-17, IL-22, and IL-23, in Inflammatory Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Ning Qu ◽  
Mingli Xu ◽  
Izuru Mizoguchi ◽  
Jun-ichi Furusawa ◽  
Kotaro Kaneko ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Th17 Cells ◽  
Functional Role ◽  
Inflammatory Diseases ◽  
Interleukin 17 ◽  
T Helper ◽  
T Helper 17 ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

T-helper 17 (Th17) cells are characterized by producing interleukin-17 (IL-17, also called IL-17A), IL-17F, IL-21, and IL-22 and potentially TNF-α and IL-6 upon certain stimulation. IL-23, which promotes Th17 cell development, as well as IL-17 and IL-22 produced by the Th17 cells plays essential roles in various inflammatory diseases, such as experimental autoimmune encephalomyelitis, rheumatoid arthritis, colitis, and Concanavalin A-induced hepatitis. In this review, we summarize the characteristics of the functional role of Th17 cells, with particular focus on the Th17 cell-related cytokines such as IL-17, IL-22, and IL-23, in mouse models and human inflammatory diseases.

scholarly journals Liver X Receptor regulates Th17 and RORγt+ Treg cells by distinct mechanisms

2019 ◽  
Author(s):  
Sara M. Parigi ◽  
Srustidhar Das ◽  
Annika Frede ◽  
Rebeca F. Cardoso ◽  
Kumar Parijat Tripathi ◽  
...  
Keyword(s):  
Lymph Node ◽  
Nuclear Receptors ◽  
Th17 Cells ◽  
Immune Modulation ◽  
Treg Cells ◽  
Liver X Receptor ◽  
Commensal Bacteria ◽  
T Helper ◽  
Mesenteric Lymph ◽  
Th Cell

AbstractThe gastrointestinal microenvironment, dominated by dietary compounds and the commensal bacteria, is a major driver of intestinal CD4+ T helper (Th) cell differentiation. Dietary compounds can be sensed by nuclear receptors (NRs) that consequently exerts pleiotropic effects including immune modulation. However, how NRs regulate distinct intestinal Th subsets remain poorly understood. Here, we found that under homeostatic condition Liver X receptor (LXR), a sensor of cholesterol metabolites, controls RORγt+ Treg and Th17 cells in the intestine draining mesenteric lymph node (MLN). Mechanistically, while lack of LXR signaling in CD11c+ myeloid cells led to an increase in RORγt+ Treg, modulation of MLN Th17 was independent of LXR signaling in either immune or epithelial cells. Of note, LXRα modulated only the Th17 cells, but not RORγt+ Treg in the MLN and horizontal transfer of microbiota between LXRα−/− and WT mice was sufficient to partially increase the MLN Th17 in WT mice. While LXRα deficiency increased the abundance of Ruminococcaceae and Lachnospiraceae bacterial families compared to the WT littermates, microbiota ablation including ablation of SFB was not sufficient to dampen LXRα-mediated expansion of MLN Th17. Altogether, our results suggest that LXR modulates RORγt+ Treg and Th17 cells in the MLN through distinct mechanisms.

scholarly journals Differential Levels of Regulatory T Cells and T-Helper-17 Cells in Women With Early and Advanced Endometriosis

2019 ◽  
Vol 104 (10) ◽  
pp. 4715-4729 ◽  
Author(s):  
Khaleque N Khan ◽  
Kazuo Yamamoto ◽  
Akira Fujishita ◽  
Hideki Muto ◽  
Akemi Koshiba ◽  
...  
Keyword(s):  
T Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
Lower Percentage ◽  
T Helper ◽  
T Helper 17 ◽  
Control Subjects ◽  
Cell Subpopulations ◽  
American Society ◽  
T Cell Subpopulations

Abstract Context Regulatory T (Treg) cells and T-helper-17 (Th17) cells may be involved in endometriosis. Information on the pattern of change in the percentages of Treg and Th17 cells in the peripheral blood (PB) and peritoneal fluid (PF) of women with early and advanced endometriosis is unclear. Objective To investigate the pattern of change in the percentages of Treg and Th17 cells in the PB and PF of women with early and advanced endometriosis. Methods We recruited 31 women with laparoscopically and histologically confirmed, revised American Society of Reproductive Medicine stage I-II endometriosis, 39 women with stage III-IV endometriosis, and 36 control subjects without visible endometriosis. PB and PF samples were collected and T-cell subpopulations analyzed by flow cytometry using specific monoclonal antibodies recognizing CD4+, CD25+, FOXP3+, and IL-17A+ markers. PF concentrations of TGF-β and IL-17 were measured by ELISA. Results The percentages of CD25+FOXP3+ Treg cells within the CD4+ T-cell population were significantly higher in the PF of women with advanced endometriosis than in either early endometriosis or in control subjects (P < 0.05 for both). A persistently lower percentage of CD4+IL-17A+ Th17 cells was found in both PB and PF of women with early and advanced endometriosis. Compared with IL-17 levels, PF levels of TGF-β were significantly higher in women with endometriosis (P = 0.01). Conclusion Our findings reconfirmed the current speculation that endometriosis is related to alteration of Treg and Th17 cells in the pelvis causing survival and implantation of ectopic endometrial lesions.

scholarly journals H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway.

1982 ◽  
Vol 156 (3) ◽  
pp. 822-833 ◽  
Author(s):  
C N Baxevanis ◽  
N Ishii ◽  
Z A Nagy ◽  
J Klein
Keyword(s):  
Lactate Dehydrogenase ◽  
T Cell ◽  
Cell Response ◽  
Cell Types ◽  
T Cell Response ◽  
T Helper ◽  
Th Cells ◽  
Th Cell ◽  
Antigen Presenting

We characterized the cell types involved in the H-2-controlled suppression of T cell response to lactate dehydrogenase B (LDHB). The suppressor effector (Tse) was found to be an Lyt-1+2+, J+ cell that recognizes antigen together with Ek molecules of antigen-presenting cells (APC). To become functional, the Tse cell requires a second signal from a nonspecific, Lyt-1+2-, J+ suppressor-inducer (Tsi) cell. The Tsi-Tse interaction is not subject to any genetic restriction. The target cell of suppression is an Lyt-1+2-, J- (most likely T helper [Th]) cell that recognizes LDHB in the context of A molecules on APC. The suppression is manifested in inhibition of the antigen-specific, A-restricted proliferation of Th cells. The interaction between Tse and Th is restricted by the A region of the H-2 complex. Because this restriction is determined by the receptor of Th cells, the mechanism of Th-Tse interaction most likely involves a concomitant recognition of LDHB and A region-controlled molecules by Th cells on the surface of Tse cells.

scholarly journals Th17 Cells in Autoimmune and Infectious Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
José Francisco Zambrano-Zaragoza ◽  
Enrique Jhonatan Romo-Martínez ◽  
Ma. de Jesús Durán-Avelar ◽  
Noemí García-Magallanes ◽  
Norberto Vibanco-Pérez
Keyword(s):  
T Cell ◽  
Autoimmune Diseases ◽  
Th17 Cells ◽  
Strong Association ◽  
Cell Subset ◽  
Cd4 T Cell ◽  
Th2 Cells ◽  
Cell Mediated Immunity ◽  
Th Cell ◽  
Th1 And Th2

The view of CD4 T-cell-mediated immunity as a balance between distinct lineages of Th1 and Th2 cells has changed dramatically. Identification of the IL-17 family of cytokines and of the fact that IL-23 mediates the expansion of IL-17-producing T cells uncovered a new subset of Th cells designated Th17 cells, which have emerged as a third independent T-cell subset that may play an essential role in protection against certain extracellular pathogens. Moreover, Th17 cells have been extensively analyzed because of their strong association with inflammatory disorders and autoimmune diseases. Also, they appear to be critical for controlling these disorders. Similar to Th1 and Th2 cells, Th17 cells require specific cytokines and transcription factors for their differentiation. Th17 cells have been characterized as one of the major pathogenic Th cell populations underlying the development of many autoimmune diseases, and they are enhanced and stabilized by IL-23. The characteristics of Th17 cells, cytokines, and their sources, as well as their role in infectious and autoimmune diseases, are discussed in this review.

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