Intestinal Dysbacteriosis-Propelled T Helper 17 Cells Activation Mediate the Perioperative Neurocognitive Disorder Induced by Anesthesia/Surgery in Aged Rats

Abstract Background: Perioperative neurocognitive disorders (PND) occur frequently in elderly patients after surgery, but the mechanism of PND is not very clear at present. It is reported that anesthesia/surgery could cause intestinal flora imbalance and induce neurocognitive impairment. However, the effect of intestinal flora on PND is poorly understood. We previously found that peripheral interleukin-17A (IL17A) destroyed the blood-brain barrier (BBB), leading to central inflammation and neurocognitive impairment. The small intestine is the main place where Th17 cells are produced. Therefore, we hypothesized that Th17 cells and IL-17 may be an important bridge for intestinal microbes to cause neuroinflammation. Methods: Exploratory laparotomy was performed to establish PND model under sevoflurane anesthesia. 16S rRNA high-throughput sequencing was used to detect the changes of intestinal flora. To explore the relationship between intestinal flora and PND, compound antibiotics were used to eliminate intestinal flora before anesthesia/surgery, and behavior tests, such as open field, Y maze, and fear conditioning tests were applied to detect the changes of memory ability and which was compared with the rats that did not receive compound antibiotics. The number of Th17 cells and Foxp3 cells was detected by flow cytometry in the Peyer's patches (PP), mesenteric lymph nodes (MLN), blood and brain. Hippocampus IL17, IL17RA, IL6 and IL10 were detected by Western blot. Hippocampus IL17, IL17R and IBA1 (ionized calcium binding adaptor molecule1) were detected by immunofluorescence. Results: Anesthesia/surgery caused intestinal flora imbalance and induced neurocognitive impairment, increased the number of Th17 cells in the PP, MLN, blood and brain, up-regulated the lever of IL17, IL17R and inflammatory factor production in the hippocampus. The administration of compound antibiotics before anesthesia/surgery evidently inhibited this effect, including decreased the number of Th17 cells, down-regulated the lever of IL17, IL17R and inflammatory factor production, and improved the memory function. In addition, we found that IL17R was co-labeled with IBA1 in a large amount in the hippocampus through immunofluorescence double-staining. Conclusion: Our study suggested that intestinal dysbacteriosis-propelled T helper 17 cells activation might play an important role in the pathogenesis of PND.

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Aberrant T Helper 17 Cells and Related Cytokines in Bone Marrow Microenvironment of Patients with Acute Myeloid Leukemia

Clinical and Developmental Immunology ◽

10.1155/2013/915873 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Tian Tian ◽

Shuang Yu ◽

Min Wang ◽

Cunzhong Yuan ◽

Hua Zhang ◽

...

Keyword(s):

Th17 Cells ◽

Myeloid Leukemia ◽

Th1 Cells ◽

T Helper ◽

Significant Elevation ◽

T Helper 17 ◽

T Helper 17 Cells ◽

Acute Myeloid ◽

Refractory Aml

In this study, we mainly investigate the role of Th17 cells, Th1 cells, and their related cytokines in the pathophysiology of AML. BM and PB were extracted from ND, CR, and relapsed-refractory AML patients and controls. Th subsets frequencies were examined by flow cytometry. BM plasma Th-associated cytokines levels were determined by ELISA. The frequencies of Th17 and Th1, and IFN-γor TGF-βconcentrations were significantly decreased in ND compared with CR patients or controls. Th17 percentage was significantly lower in BM than in PB for ND patients but was higher in BM for CR patients. However, in CR or relapsed-refractory patients, Th1 percentage in BM was higher than that in PB. Moreover, BM IL-17A level showed a decreased trend in ND patients. A significant elevation of plasma IL-6 level was found in ND compared with CR patients or controls. IL-17A showed the positive correlation with IL-6 concentration. And Th17 cells frequencies and TGF-β1 concentration were increased in BM from AML patients achieving CR after chemotherapy. Moreover, a significant decrease of BM plasma TGF-β1 level was found in M3 patients compared with the other subtypes. Our findings suggest that Th17 and related cytokines may be implicated in AML pathogenesis.

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Upregulated TNFR Family Member Insufficient to Promote Apoptotic Cell Death in T Helper 17 Cells

Proceedings ◽

10.3390/proceedings2251526 ◽

2018 ◽

Vol 2 (25) ◽

pp. 1526

Author(s):

Tufan Utku Çalışkan ◽

Ayten Nalbant

Keyword(s):

T Cells ◽

Cell Death ◽

Cd4 T Cells ◽

Th17 Cells ◽

Apoptotic Cell ◽

B Cell Lymphoma ◽

Apoptotic Cell Death ◽

T Helper ◽

T Helper 17 ◽

T Helper 17 Cells

Fas is the receptor of tumor necrosis family receptors (TNFR) and involves in apoptosis. Since discovery of T helper 17 cells (Th17) in 2005, which are defined as a new type of helper T cells, it has become clear that the dysregulated function Th17 cells and their cytokines could contribute to pathology of diseases including autoimmune diseases and cancer. There is not much known about apoptotic and survival mechanisms of Th17 cells in the literature. Therefore, the players of apoptotic cell death in Th17 cells were investigated in the study. To carry out designed experiments, venous blood were drawn from the healthy volunteers with approval from the Noninvasive Ethics Committee. Peripheral blood mononuclear cells (PBMCs) were isolated from blood with Ficoll separation method. The naïve CD4+ T cells were sorted from the PBMC. Sorted naive T cells were cultured under Th17 polarizing conditions. The activation, differentiation and apoptosis related molecules of cultured cells were monitored by Flow cytometry. Data showed that naive CD4+ T cells were activated and differentiated into Th17 cells. Activated Th17 cells were Fas positive. Activated, Fas positive Th17 cells did not underwent significant plasma membrane changes. Furthermore, it was also observed that there was not much change in the Bcl-2 protein level. Bcl-2 protein is belongs to B-cell-lymphoma-2 (Bcl-2) family proteins and is major regulator of intrinsic apoptotic pathway as promoting cell survival. In addition to that the expression of Bclx-L, is an anti-apoptotic protein, were increased in these cells. Data indicates that Th17 cells (under Th17 polarization condition) were increased expression of anti-apoptotic Bcl-2 family members.

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