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10.1038/s41467-020-18184-3 http://scihub22266oqcxt.onion/10.1038/s41467-020-18184-3 32868758!7459119!32868758     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nat+Commun 2020 ; 11 (1): 4368 Nephropedia Template TP {{tp|p=32868758|t=2020. Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses |pdf=|usr=}}{{32868758}} gab.com Text Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=32868758 #FOAvip Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by (23)Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown. Twit Text FOAVip Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=32868758 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32868758 #FOAvip English Wikipedia <ref>{{Cite pmid|32868758}}</ref> Inherited salt-losing tubulopathies are associated with immunodeficiency due to impaired IL-17 responses #MMPMID32868758 Evans RDR; Antonelou M; Sathiananthamoorthy S; Rega M; Henderson S; Ceron-Gutierrez L; Barcenas-Morales G; Muller CA; Doffinger R; Walsh SB; Salama AD Nat Commun 2020[Aug]; 11 (1): 4368 PMID32868758show ga Increased extracellular sodium activates Th17 cells, which provide protection from bacterial and fungal infections. Whilst high salt diets have been shown to worsen autoimmune disease, the immunological consequences of clinical salt depletion are unknown. Here, we investigate immunity in patients with inherited salt-losing tubulopathies (SLT). Forty-seven genotyped SLT patients (with Bartter, Gitelman or EAST Syndromes) are recruited. Clinical features of dysregulated immunity are recorded with a standardised questionnaire and immunological investigations of IL-17 responsiveness undertaken. The effects of altering extracellular ionic concentrations on immune responses are then assessed. Patients are hypokalaemic and hypomagnesaemic, with reduced interstitial sodium stores determined by (23)Na-magnetic resonance imaging. SLT patients report increased mucosal infections and allergic disease compared to age-matched controls. Aligned with their clinical phenotype, SLT patients have an increased ratio of Th2:Th17 cells. SLT Th17 and Tc17 polarisation is reduced in vitro, yet STAT1 and STAT3 phosphorylation and calcium flux following T cell activation are unaffected. In control cells, the addition of extracellular sodium (+40 mM), potassium (+2 mM), or magnesium (+1 mM) reduces Th2:Th17 ratio and augments Th17 polarisation. Our results thus show that the ionic environment typical in SLT impairs IL-17 immunity, but the intracellular pathways that mediate salt-driven Th17 polarisation are intact and in vitro IL-17 responses can be reinvigorated by increasing extracellular sodium concentration. Whether better correction of extracellular ions can rescue the immunophenotype in vivo in SLT patients remains unknown. |Adolescent[MESH] |Adult[MESH] |Aged, 80 and over[MESH] |Animals[MESH] |Child, Preschool[MESH] |Chronic Disease[MESH] |Cohort Studies[MESH] |Female[MESH] |Genetic Diseases, Inborn[MESH] |Humans[MESH] |Immunologic Deficiency Syndromes/*etiology[MESH] |Interleukin-17/*metabolism[MESH] |Kidney Tubules, Distal/*pathology[MESH] |Magnesium/metabolism[MESH] |Male[MESH] |Middle Aged[MESH] |Potassium/metabolism[MESH] |Salts/metabolism/therapeutic use[MESH] |Sodium Chloride, Dietary/therapeutic use[MESH] |Sodium Chloride/metabolism[MESH] |Sodium/metabolism[MESH] |Th17 Cells/metabolism[MESH] |Th2 Cells/metabolism[MESH]Inherited salt-losing tubulopathies are associated with immunodeficien(epmc).pdf DeepDyve Pubget Overpricing