Helminthes Infection enhances GAS6 expression dampening Th17 development in patients with Multiple Sclerosis

ORTIZ WILCZYÑSKI, JUAN MANUEL; OLEXEN, CINTHIA MARIEL; ERRASTI, ANDREA EMILSE; SCHATTNER, MIRTA; ROTHLIN CARLA V; CORREALE JORGE; CARRERA SILVA, EUGENIO ANTONIO

Ciudad del Cabo

Simposio; Keystone Symposia on Molecular and Cellular Biology. Helminths: New Insights from Immunity to Global Health; 2019

Helminth infections are known to modulate the courseof inflammatory and autoimmune diseases due to their ability to triggerregulatory mechanisms in the hosts, a phenomenon that results advantageous insuch pathological context (Correale and Farez, 2007; Elliott, et al.; 2007; Flemingand Weinstock, 2012). The tyrosine kinasereceptors TYRO3, AXL, and MERTK (TAM) have been described as inhibitors of the immuneresponse in type I and type II inflammatory settings (Rothlin et al.,2007; CarreraSilva et al., 2013; Chanet al., 2016). Here, we test ifhelminth infections engage the TAM axis in patients with Multiple Sclerosis andinfluence the adaptive immune response. The TAM receptor agonist GAS6 but notPROS1 was up-regulated in circulating CD4+ T and CD11b+ cells from patientswith Multiple Sclerosis that were concomitantly infected with helminthes (HIMS)compared to healthy donors (Control) or uninfected Multiple Sclerosis (MS) patients.Interestingly, when T cells were simulated with α-CD3/α-CD28 for 7 to 10 daysin vitro, HIMS samples showed lower percentage of Th17 cells compared to samplesfrom non-infected MS individuals or healthy donors. Given that both GAS6 andPROS1 need to bind phosphatidylserine (PS) in a Ca++ dependent manner to effectivelyactivate TAM receptors, we blocked exposed PS by using Annexin V during T cellculture. The reduction of PS availability in activated T cells induced an increasedpercentage of IL-17 expressing cells together with higher levels of homing celladhesion molecule CD44, but a decreased proliferation rate and CD25 expression.Similarly, blocking GAS6 with a monoclonal antibody induced an expansion of Th17subset. Our results suggest that GAS6 is differentially induced during type 2immunity and contribute to dampen Th17 development. This research was supportedby CONICET and the ANPCyT, Argentina<!-- /* Font Definitions */@font-face{font-family:Arial;panose-1:2 11 6 4 2 2 2 2 2 4;mso-font-charset:0;mso-generic-font-family:auto;mso-font-pitch:variable;mso-font-signature:3 0 0 0 1 0;}@font-face{font-family:"ＭＳ 明朝";panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-charset:128;mso-generic-font-family:roman;mso-font-format:other;mso-font-pitch:fixed;mso-font-signature:1 134676480 16 0 131072 0;}@font-face{font-family:"ＭＳ 明朝";panose-1:0 0 0 0 0 0 0 0 0 0;mso-font-charset:128;mso-generic-font-family:roman;mso-font-format:other;mso-font-pitch:fixed;mso-font-signature:1 134676480 16 0 131072 0;} /* Style Definitions */p.MsoNormal, li.MsoNormal, div.MsoNormal{mso-style-unhide:no;mso-style-qformat:yes;mso-style-parent:"";margin:0cm;margin-bottom:.0001pt;mso-pagination:widow-orphan;layout-grid-mode:char;font-size:10.0pt;font-family:"Times New Roman";mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-bidi-font-family:"Times New Roman";mso-ansi-language:EN-US;}.MsoChpDefault{mso-style-type:export-only;mso-default-props:yes;font-family:Cambria;mso-ascii-font-family:Cambria;mso-ascii-theme-font:minor-latin;mso-fareast-font-family:"ＭＳ 明朝";mso-fareast-theme-font:minor-fareast;mso-hansi-font-family:Cambria;mso-hansi-theme-font:minor-latin;mso-bidi-font-family:"Times New Roman";mso-bidi-theme-font:minor-bidi;}@page WordSection1{size:612.0pt 792.0pt;margin:72.0pt 90.0pt 72.0pt 90.0pt;mso-header-margin:36.0pt;mso-footer-margin:36.0pt;mso-paper-source:0;}div.WordSection1{page:WordSection1;}-->