Faculty Opinions recommendation of Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity.

2021 ◽  
Author(s):  
Vanja Lazarevic
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Effector T Cells

scholarly journals Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments

Blood ◽  
2009 ◽  
Vol 114 (6) ◽  
pp. 1141-1149 ◽  
Author(s):  
Ilona Kryczek ◽  
Mousumi Banerjee ◽  
Pui Cheng ◽  
Linhua Vatan ◽  
Wojciech Szeliga ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Regulatory T Cells ◽  
Cancer Patients ◽  
Th17 Cells ◽  
Human Tumor ◽  
Active Role ◽  
Effector T Cells ◽  
Cell Phenotype ◽  
Effector Cells

Abstract Th17 cells play an active role in autoimmune diseases. However, the nature of Th17 cells is poorly understood in cancer patients. We studied Th17 cells, the associated mechanisms, and clinical significance in 201 ovarian cancer patients. Tumor-infiltrating Th17 cells exhibit a polyfunctional effector T-cell phenotype, are positively associated with effector cells, and are negatively associated with tumor-infiltrating regulatory T cells. Tumor-associated macrophages promote Th17 cells through interleukin-1β (IL-1β), whereas tumor-infiltrating regulatory T cells inhibit Th17 cells through an adenosinergic pathway. Furthermore, through synergistic action between IL-17 and interferon-γ, Th17 cells stimulate CXCL9 and CXCL10 production to recruit effector T cells to the tumor microenvironment. The levels of CXCL9 and CXCL10 are associated with tumor-infiltrating effector T cells. The levels of tumor-infiltrating Th17 cells and the levels of ascites IL-17 are reduced in more advanced diseases and positively predict patient outcome. Altogether, Th17 cells may contribute to protective human tumor immunity through inducing Th1-type chemokines and recruiting effector cells to the tumor microenvironment. Inhibition of Th17 cells represents a novel immune evasion mechanism. This study thus provides scientific and clinical rationale for developing novel immune-boosting strategies based on promoting the Th17 cell population in cancer patients.

scholarly journals Combinatory treatment using tacrolimus and a STAT3 inhibitor regulate Treg cells and plasma cells

2018 ◽  
Vol 32 ◽  
pp. 205873841877872 ◽  
Author(s):  
Jin-Sil Park ◽  
Sung-Min Kim ◽  
Sun-Hee Hwang ◽  
Si-Young Choi ◽  
Ji Ye Kwon ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lupus Erythematosus ◽  
Th17 Cells ◽  
Plasma Cells ◽  
Treg Cells ◽  
Interferon Γ ◽  
Effector T Cells ◽  
Circulating Autoantibodies

Systemic lupus erythematosus (SLE; lupus) is a prototypical autoimmune disease characterized by circulating autoantibodies to nuclear antigens and immune complex deposition, resulting in damage to target organs. To investigate the effects of tacrolimus (TAC) on effector T cells and B cells, we examined its involvement in the development of effector T cells, germinal center (GC) B cells, and plasma cells in an in vitro system using wild-type (WT) and lupus-prone mice. The population of T helper (Th) 1, Th2, and Th17 cells interleukin (IL)-17-producing T (Th17) cells and the production of interferon-γ and interleukin-17A IL-17A were suppressed by TAC. TAC also reduced the population of regulatory T (Treg) cells; however, a combination treatment with the signal transducer and activator of transcription 3 (STAT3) inhibitor STA-21 promoted the population of Treg cells. TAC also suppressed the populations of GC B cells and plasma cells synergistically with STA-21. These findings suggest that the application of TAC with a STAT3 signal inhibitor may provide benefits in SLE treatment.

scholarly journals NIK signaling in dendritic cells but not in T cells is required for the development of effector T cells and cell-mediated immune responses

2011 ◽  
Vol 208 (9) ◽  
pp. 1917-1929 ◽  
Author(s):  
Janin Hofmann ◽  
Florian Mair ◽  
Melanie Greter ◽  
Marc Schmidt-Supprian ◽  
Burkhard Becher
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Cd4 T Cells ◽  
Driving Force ◽  
Th17 Cells ◽  
Effector T Cells ◽  
Cell Mediated Immunity ◽  
Systematic Analysis

The canonical NF-κB pathway is a driving force for virtually all aspects of inflammation. Conversely, the role of the noncanonical NF-κB pathway and its central mediator NF-κB–inducing kinase (NIK) remains poorly defined. NIK has been proposed to be involved in the formation of TH17 cells, and its absence in TH cells renders them incapable of inducing autoimmune responses, suggesting a T cell–intrinsic role for NIK. Upon systematic analysis of NIK function in cell-mediated immunity, we found that NIK signaling is dispensable within CD4+ T cells but played a pivotal role in dendritic cells (DCs). We discovered that NIK signaling is required in DCs to deliver co-stimulatory signals to CD4+ T cells and that DC-restricted expression of NIK is sufficient to restore TH1 and TH17 responses as well as cell-mediated immunity in NIK−/− mice. When CD4+ T cells developed in the absence of NIK-sufficient DCs, they were rendered anergic. Reintroduction of NIK into DCs allowed developing NIK−/− CD4+ T cells to become functional effector populations and restored the development of autoimmune disease. Therefore, our data suggest that a population of thymic DCs requires NIK to shape the formation of most αβ CD4+ T effector lineages during early development.

scholarly journals High intensity focused ultrasound enhances anti-tumor immunity through promoting CD4 Th1 effector T cell response

STEMedicine ◽  
2020 ◽  
Vol 1 (4) ◽  
pp. e65 ◽  
Author(s):  
Haiying Zhang ◽  
Kun Han
Keyword(s):  
T Cells ◽  
Tumor Immunity ◽  
High Intensity ◽  
Th17 Cells ◽  
Focused Ultrasound ◽  
Transforming Growth Factor ◽  
Effector T Cells ◽  
T Cell Response ◽  
High Intensity Focused Ultrasound ◽  
Luciferase Assay

Background: Melanoma accounts for more than 80% of deaths from all dermatologic cancers, mainly due to its widespread metastasis. High intensity focused ultrasound (HIFU) is a promising technique for cancer therapy. Here, we investigated the efficacy of HIFU against melanoma and the underlying mechanisms. Methods: A melanoma allograft mouse model was established to examine the tumor progression and survival rate. Anti-tumor immunity was determined by measuring cytokines, regulatory T cells (Tregs), Th17 cells and CD8+ effector T cells. Western blot, qPCR, RNAi and luciferase assay were performed to confirm the expression and regulation of microRNA (miR)-9-5p and transforming growth factor beta (TGF-β). Results: HIFU exposure significantly suppressed melanoma growth and metastasis by activating interferon gamma (IFN-γ) secretion, inhibiting Tregs and Th17 cells, and stimulating CD8+ effector T cells. TGF-β was a direct target of miR-9-5p. The anti-tumor effect of HIFU might be mediated through the miR-9-5p/TGF-β pathway. Conclusion: HIFU activates anti-tumor response and alters tumor microenvironment, which may serve as a potential therapeutic strategy for melanoma treatment.

Stem-like intestinal Th17 cells give rise to pathogenic effector T cells during autoimmunity

Cell ◽  
2021 ◽  
Author(s):  
Alexandra Schnell ◽  
Linglin Huang ◽  
Meromit Singer ◽  
Anvita Singaraju ◽  
Rocky M. Barilla ◽  
...  
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Effector T Cells

scholarly journals Nine lives: plasticity among T helper cell subsets

2009 ◽  
Vol 206 (8) ◽  
pp. 1643-1646 ◽  
Author(s):  
Richard M. Locksley
Keyword(s):  
T Cells ◽  
Division Of Labor ◽  
Th17 Cells ◽  
Effector T Cells ◽  
T Helper Cell ◽  
Th2 Cells ◽  
T Helper ◽  
Molecular Context ◽  
Initial Description ◽  
Th1 And Th2

The division of labor among two types of T helper (Th) subsets, first described over 20 yr ago, has been buffeted by the discovery of new subsets and new cytokines that can be coaxed out of T cells with increasing disregard for the subset of origin. Although Th17 cells and regulatory T (T reg) cells are widely accepted subsets, and others are being proposed, their plasticity is difficult to reconcile with the definitions of Th subsets as put forth in the initial description of Th1 and Th2 cells. A deeper molecular context will be required to reconcile the ever-increasing complexity of effector T cells.

scholarly journals Th17 cells: Effector T cells with inflammatory properties

2007 ◽  
Vol 19 (6) ◽  
pp. 362-371 ◽  
Author(s):  
Thomas Korn ◽  
Mohamed Oukka ◽  
Vijay Kuchroo ◽  
Estelle Bettelli
Keyword(s):  
T Cells ◽  
Th17 Cells ◽  
Effector T Cells

scholarly journals P038 Microbial regulation of T-cell fate towards regulatory profiles during T-cell transfer induced colitis

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S150-S151
Author(s):  
A Machicote ◽  
P Pelczar ◽  
M Nawrocki ◽  
A Fazio ◽  
B Liu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Antibiotic Treatment ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Treg Cells ◽  
Effector T Cells ◽  
Cell Transfer ◽  
Cell Plasticity ◽  
T Cell Transfer

Abstract Background During Inflammatory Bowel Diseases (IBD), CD4+ effector T cells are main mediators of the tissue damage. Among them, Th17 cells strongly contribute to the inflammatory response. Interestingly, our lab previously showed that Th17 cells can convert into regulatory T cells, thereby controlling inflammation. However, the forces controlling the plasticity of T cells during IBD remain largely unknown. Our aim is to understand, how CD4+ T-cell plasticity can be modulated from a pro-inflammatory towards an anti-inflammatory profile during IBD. It is currently known that both Th17 and Foxp3 Treg cells can recognize microbiota-derived antigens and that changes in the microbiota are commonly observed in IBD. We hypothesize that the microbiota is a key candidate to modulate T-cell plasticity. Methods T-cell transfer mouse IBD model was performed by transferring CD4+ naïve T-cells into Rag1 -/- receptors. To study Th17 T-cell plasticity, we used as donors IL-17A Fate-mapping mice. These mice comprise of an IL-17ACRE/R26fl/fl YFP construct where the cells that previously expressed IL-17A turn into YFP+ cells. Ciprofloxacin and metronidazole, two antibiotics commonly given to IBD patients, were used to treat the mice. Stool microbiota composition was analysed longitudinally by 16S rRNA amplicon sequencing. Colitis development was evaluated by colonoscopy. CD4+ T cells were isolated from the colon and reporter expression was analysed by Flow Cytometry. Results After T-cell transfer colitis induction, ciprofloxacin and metronidazole treatment alleviated gut inflammation, as determined by weight loss (p=0.005), colitis score (p=0.004) and colon length (p=0.01). Antibiotic treatment increased the relative abundance of bacteria previously associated with beneficial IBD outcomes (e.g. Bifidobacterium). Interestingly, colonic CD4+ T-cells showed an increased conversion from Th17 towards a Foxp3+ Treg profile (Foxp3ExTh17) (p=0.03). Conclusion The conversion of CD4+ effector T cells into Treg cells is a promising approach to counteract inflammation in IBD patients. We showed that antibiotic treatment not only correlates with a relative expansion of beneficial bacteria, but perhaps most interesting, with an increased conversion of effector Th17 cells towards Foxp3+ Treg cells in the colon. Altogether, these data support the manipulation of the microbiota as a tool to revert intestinal inflammation in IBD patients.

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