TH17

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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TH17

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T-helper cell 17 (TH17)
©2020 PFPC

COVID-19

De Biasi S, Meschiari M, Gibellini L, Bellinazzi C, Borella R, Fidanza L, Gozzi L, Iannone A, Lo Tartaro D, Mattioli M, Paolini A, Menozzi M, Milić J, Franceschi G, Fantini R, Tonelli R, Sita M, Sarti M, Trenti T, Brugioni L, Cicchetti L, Facchinetti F, Pietrangelo A, Clini E, Girardis M, Guaraldi G, Mussini C, Cossarizza A - "Marked T cell activation, senescence, exhaustion and skewing towards TH17 in patients with COVID-19 pneumonia" Nat Commun 11(1):3434 (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338513/

Muyayalo KP, Huang DH, Zhao SJ, Xie T, Mor G, Liao AH - "COVID-19 and Treg/Th17 imbalance: Potential relationship to pregnancy outcomes" Am J Reprod Immunol. e13304 (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6307942/

Ayhan E, Öztürk M, An İ, Abdelmaksoud A, Araç E - "Potential role of Anti-IL-17 in COVID-19 treatment" Dermatol Ther May 30:e13715 (2020) doi: 10.1111/dth.13715. Epub ahead of print. PMID: 32475041

Casillo GM, Mansour AA, Raucci F, Saviano A, Mascolo N, Iqbal AJ, Maione F - "Could IL-17 represent a new therapeutic target for the treatment and/or management of COVID-19-related respiratory syndrome?" Pharmacol Res 156:104791 (2020) doi: 10.1016/j.phrs.2020.104791. Epub 2020 Apr 14. PMID: 32302707; PMCID: PMC7194796
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194796/

Wu D, Yang XO - "TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib" J Microbiol Immunol Infect 53(3):368–70 (2020) doi: 10.1016/j.jmii.2020.03.005. Epub ahead of print. PMID: 32205092; PMCID: PMC7156211
https://pubmed.ncbi.nlm.nih.gov/25732870/

Fluoride

Zhu SQ, Zhou BH, Tan PP, Chai J, Yu YM, Wang HW - "Based on G-Series Mouse TH17 Array Study the Effect of Fluoride on C2C12 Cells Cytokines Expression" Biol Trace Elem Res (2020) doi: 10.1007/s12011-020-02464-6. Epub ahead of print. PMID: 33244669
https://pubmed.ncbi.nlm.nih.gov/33244669/
"The results indicated that fluoride might induce cytotoxicity by disturbing Th17-related cytokine expression."

Quadri JA, Sarwar S, Pinky, Kar P, Singh S, Mallick SR, Arava S, Nag TC, Roy TS, Shariff A - "Fluoride induced tissue hypercalcemia, IL-17 mediated inflammation and apoptosis lead to cardiomyopathy: Ultrastructural and biochemical findings" Toxicology 406-407:44-57 (2018) doi: 10.1016/j.tox.2018.05.012. Epub 2018 May 22. PMID: 29800585
https://pubmed.ncbi.nlm.nih.gov/29800585

"Fluoride induces apoptosis and autophagy through the IL-17 signaling pathway in mice hepatocytes"


(Zhao et al., 2018)

Zhao Y, Li Y, Wang J, Manthari RK, Wang J - "Fluoride induces apoptosis and autophagy through the IL-17 signaling pathway in mice hepatocytes" Arch Toxicol 92(11):3277-3289 (2018) doi: 10.1007/s00204-018-2305-x. Epub 2018 Sep 17. PMID: 30225638
https://pubmed.ncbi.nlm.nih.gov/30225638/

Guo H, Kuang P, Luo Q, Cui H, Deng H, Liu H, Lu Y, Fang J, Zuo Z, Deng J, Li Y, Wang X, Zhao L - "Effects of sodium fluoride on blood cellular and humoral immunity in mice" Oncotarget 8(49):85504-85515 (2017)
https://www.ncbi.nlm.nih.gov/pmc/articl ... /29156736/

Gq/11

Gq/11 negatively control the differentiation of Th17 cells.

He Y, Huang Y, Tu L, Luo J, Yu B, Qian H, Duan L, Shi G - "Decreased Gαq expression in T cells correlates with enhanced cytokine production and disease activity in systemic lupus erythematosus" Oncotarget 7(52):85741-85749 (2016)
https://www.oncotarget.com/article/13903/text/
"These data suggest that reduced Gαq levels in T cells may promote enhanced and prolonged T cell activation, contributing to the clinical manifestations of SLE."

Lai W, Cai Y, Zhou J, Chen S, Qin C, Yang C, Liu J, Xie X, Du C - "Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation" Cell Mol Immunol 14(6):557-567 (2017)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518818/

Liu Y, Wang D, Li F, Shi G - "Gαq controls rheumatoid arthritis via regulation of Th17 differentiation" Immunol Cell Biol 93(7):616-24 (2015)
https://onlinelibrary.wiley.com/doi/abs ... cb.2015.13

McAleer JP, Fan J, Roar B, Primerano DA, Denvir J - "Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors" Sci Rep 8(1):10954 (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053392/

Qian H, Wang M, Wang Y, Ying W, Zhang J, Huan Y, He Y, Liu Y, Shi G - "Role of Galphaq in pathogenesis of psoriasis, a new mechanism about the immune regulation in psoriasis" Int Immunopharmacol 68:185-192 (2019)
https://pubmed.ncbi.nlm.nih.gov/30654308/
"Our results indicated that Gαq was involved in the pathogenesis of PSO, and its regulation on Th17 cell differentiation and cytokine production."

McAleer JP, Fan J, Roar B, Primerano DA, Denvir J - "Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors" Sci Rep 8(1):10954 (2018) doi: 10.1038/s41598-018-29262-4. PMID: 30026493; PMCID: PMC6053392
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6053392/

Noubade R, Krementsov DN, Del Rio R, Thornton T, Nagaleekar V, Saligrama N, Spitzack A, Spach K, Sabio G, Davis RJ, Rincon M, Teuscher C - "Activation of p38 MAPK in CD4 T cells controls IL-17 production and autoimmune encephalomyelitis" Blood 118(12):3290-300 (2011) doi: 10.1182/blood-2011-02-336552. Epub 2011 Jul 25. PMID: 21791428; PMCID: PMC3179398
https://pubmed.ncbi.nlm.nih.gov/21791428/

Thyroid

Konca Degertekin C, Aktas Yilmaz B, Balos Toruner F, Kalkanci A, Turhan Iyidir O, Fidan I, Yesilyurt E, Cakır N, Kustimur S, Arslan M - "Circulating Th17 cytokine levels are altered in Hashimoto's thyroiditis" Cytokine 80:13-7 (2016) doi: 10.1016/j.cyto.2016.02.011. Epub 2016 Feb 27. PMID: 26928603
https://www.sciencedirect.com/science/a ... 6616300357

Figueroa-Vega N, Alfonso-Pérez M, Benedicto I, Sánchez-Madrid F, González-Amaro R, Marazuela M - "Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto's thyroiditis" J Clin Endocrinol Metab 95(2):953-62 (2010) doi: 10.1210/jc.2009-1719. Epub 2009 Dec 16. PMID: 20016049
https://pubmed.ncbi.nlm.nih.gov/20016049/

Vitales-Noyola M, Ramos-Levi AM, Martínez-Hernández R, Serrano-Somavilla A, Sampedro-Nuñez M, González-Amaro R, Marazuela M - "Pathogenic Th17 and Th22 cells are increased in patients with autoimmune thyroid disorders" Endocrine 57(3):409-417 (2017)
https://pubmed.ncbi.nlm.nih.gov/28669056/

He L, Zhu X, Yang Q, Li X, Huang X, Shen C, Liu J, Zha B - "Low Serum IL-17A in Pregnancy During Second Trimester Is Associated With an Increased Risk of Subclinical Hypothyroidism" Front Endocrinol (Lausanne) 11:298 (2020)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7239996/
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