When worlds collide: Th17 and Treg cells in cancer and autoimmunity

Knochelmann, Hannah M.; Dwyer, Connor J.; Bailey, Stefanie R.; Amaya, Sierra M.; Elston, Dirk M.; Mazza-McCrann, Joni; Paulos, Chrystal M.

doi:10.1038/s41423-018-0004-4

Cited by 392 publications

(337 citation statements)

References 218 publications

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“…17 If future studies confirm the association of these bacteria with human disease, the possibility of regulating their growth with pre-or probiotics must be considered. 3 In fact, decreased levels of Tregs have been demonstrated in patients with alopecia areata. 19 Short-chain fatty acids (SCFAs) are produced by gut bacteria after fermentation of dietary fibre.…”

Section: Discussionmentioning

confidence: 99%

“…1 This loss of immune privilege could be due to environmental triggers or dysregulation of the immune system. 3,4 Furthermore, increased levels of Th17 cells and decreased levels of Treg cells have been found in alopecia areata patients. 3,4 Furthermore, increased levels of Th17 cells and decreased levels of Treg cells have been found in alopecia areata patients.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers

Moreno‐Arrones

Serrano‐Villar²,

Pérez‐Brocal

et al. 2019

Acad Dermatol Venereol

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Background Alopecia areata is a T‐cell‐mediated autoimmune disease with an unknown etiopathogenesis. Gut microbiota has been revealed as a key modulator of systemic immunity. Objective To determine whether patients affected by alopecia universalis present differences in gut bacteria composition compared with healthy controls and investigate possible bacterial biomarkers of the disease. Methods We conducted a cross‐sectional study that involved 15 patients affected by alopecia universalis and 15 controls. Gut microbiome of the study subjects was analysed by sequencing the 16SrRNA of stool samples. We searched for bacterial biomarkers of alopecia universalis using the linear discriminant analysis effect size (LEFse) tool. Results In total, 30 study subjects (46.6% female; mean [SD] age, 40.1 [9.8] years) were enrolled. Neither alpha (Shannon diversity index 5.31 ± 0.43 vs. 5.03 ± 0.43, P 0.1) or beta diversity (ADONIS P value: 0.35) of gut microbiota showed statistically significant differences between cases and controls. In patients affected with alopecia, we found an enriched presence (LDA SCORE > 2) of Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis. A predictive model based on the number of bacterial counts of Parabacteroides distasonis and Clostridiales vadin BB60 group correctly predicted disease status in 80% of patients (AUC 0.804 (0.633–0.976), P 0.004). Conclusion Alopecia universalis does not seem to affect broadly gut microbiota structure. Bacterial biomarkers found associated with the disease (Holdemania filiformis, Erysipelotrichacea, Lachnospiraceae, Parabacteroides johnsonii, Eggerthellaceae, Clostridiales vadin BB60 group, Bacteroides eggerthii and Parabacteroides distasonis) should be further studied as they could be involved in its pathophysiology or be used as diagnostic tools.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers

Moreno‐Arrones

Serrano‐Villar²,

Pérez‐Brocal

et al. 2019

Acad Dermatol Venereol

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“…During the past 10 years, the Th1/Th2 paradigm has been expanded into the Th1/Th2/Th17 and Treg cell paradigm. Th17 cells play a complex and controversial role in tumor immunity and have been found to exhibit a fluctuating identity within the context of cancer [100]. Treg cells are required for self-tolerance and defense against autoimmunity and often correlate with cancer progression.…”

Section: The New Hypothesismentioning

confidence: 99%

“…Treg cells are required for self-tolerance and defense against autoimmunity and often correlate with cancer progression. Treg cells are currently known to inhibit proliferation and cytokine production by both CD4+ and CD8+ T cells, immunoglobulin production by B cells, cytotoxic activity of the natural killer cells, as well as maturation of dendritic cells, resulting in induction of immunological tolerance [99, 100]. …”

Section: The New Hypothesismentioning

confidence: 99%

HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas – Why?

Syrjänen

2019

Acta Cytologica

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Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982–1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies. Summary: In this review, the authors first describe the scope (i.e., HNSCC) by the anatomic sites of the tumors. Their important site-specific differences in epidemiology are emphasized, and the misconceptions caused by the adopted practice of pooling all tumors from these divergent anatomic sites as a single entity (HNSCC) are pinpointed. The convincing evidence of the established risk factors (smoking and alcohol) is briefly addressed, before entering in the discussion on the causal role of HPV in HNSCC pathogenesis. The global HPV prevalence in different subsets of HNSCC is summarized using the data extracted from all meta-analyses published since 2010. Of all HNSCC subsets, oropharyngeal SCC has an HPV profile distinct form all the other subsets, and the possible mechanisms explaining this intimate association with HPV are discussed. Key Messages: Recent global trends show a constant increase in HNSCC rates particularly among younger age groups. The evidence on cigarette smoking and alcohol consumption as the prime risk factors of HNSCC is overwhelming. During the past 35 years, however, increasing evidence has accumulated implicating an important causal role of HPV in HNSCC. These data have important clinical implications, HPV detection and tailored treatment strategies for HPV-positive HNSCCs currently being an integral part of the oncological management practices of HNSCC.

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“…TGF‐β1 signaling pathway plays a dichotomous role in the balance of Th17 and Treg and acts as a link between Th17 and Foxp3 + Treg cells . Under physiological conditions, TGF‐β1 up‐regulates the expression of both Foxp3 (transcription factor for Treg cells) and RORγt (Th17 cell transcription factor) in natural CD4+ T cells.…”

Section: Discussionmentioning

confidence: 99%

Effects of thalidomide on Th17, Treg cells and TGF‐β1/Smad3 pathway in a mouse model of systemic sclerosis

et al. 2019

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Objective To evaluate the immune regulatory and anti‐fibrosis function of thalidomide (Thal) in systemic sclerosis (SSc), we investigated the effects of Thal on: (a) Th17 and Treg cell production; (b) related factors expression; and (c) transforming growth factor (TGF)‐β1/Smad3 pathway, using a mouse model of SSc. Methods Forty female BALB/c mice were randomly divided into a normal control (NC) group, SSc group (bleomycin [BLM]‐induced experimental SSc), BLM + Thal (10 mg/kg/day) group, BLM + Thal (20) group, and BLM + Thal (30) group. Thal was administered a day after BLM. At the end of the animal experiments, mouse tissues were collected for detection of pathological changes and hydroxyproline content. Flow cytometry, real‐time polymerase chain reaction, enzyme‐linked immunosorbent assay, immunohistochemistry, Western blot and other methods were used to measure Th17, Treg cell population and their related factors, as well as TGF‐β1/Smad3 pathway expression. Results Thal treatment: (a) reduced skin, and pulmonary tissue fibrosis, inflammation score, and hydroxyproline content (P < .001) in BLM‐induced SSc mice; (b) reduced the percentages of Th17 cells and associated interleukin (IL)‐17A expression (both P < .05) but increased the percentages of Treg cells and its transcription factor Foxp3 expression (both P < .05); (c) correlation analysis found positive correlations between Th17/Treg ratio, the inflammatory score of the skin and pulmonary tissues, hydroxyproline content, and type I collagen messenger RNA expression (r = .8546, .8656, .6902, .6807, .8118, and .8424, respectively, P < .01); (d) Thal inhibited TGF‐β1 expression and Smad3 phosphorylation (both P < .05); (e) TGF‐β1 was positively correlated with the IL‐17A and Th17/Treg ratio (r = .5856, P = .005; r = .6684, P = .0107, respectively). Conclusion Thal can effectively prevent skin and pulmonary tissue fibrosis in a mouse model of SSc through the TGF‐β1/Smad3 signaling pathway and can rectify the distortion of the Th17/Treg balance in SSc by potentially regulating Th17 and Treg cell production, as well as their related factors expression.

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When worlds collide: Th17 and Treg cells in cancer and autoimmunity

Cited by 392 publications

References 218 publications

Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers

Analysis of the gut microbiota in alopecia areata: identification of bacterial biomarkers

HPV in Head and Neck Carcinomas: Different HPV Profiles in Oropharyngeal Carcinomas – Why?

Effects of thalidomide on Th17, Treg cells and TGF‐β1/Smad3 pathway in a mouse model of systemic sclerosis

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