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Front. Cell Dev. Biol. | doi: 10.3389/fcell.2018.00158

THY-1 (CD90) SIGNALING PREFERENTIALLY PROMOTES MOUSE TH2 AND TH17 CD4+ T CELL DEVELOPMENT

 David Hoskin1*, Suzanne Furlong1 and  Melanie Coombs2
  • 1Dalhousie University, Canada
  • 2Acadia University, Canada

Thy-1 (CD90) is a glycosylphosphatidylinositol-anchored protein (GPI-AP) with signaling properties that is abundant on mouse T cells. Upon antibody-mediated crosslinking, Thy-1 provides a T cell receptor (TcR)-like signal that is sufficient to drive CD4+ T cell proliferation and differentiation into effector cells when costimulatory signals are provided by syngeneic lipopolysaccharide-matured bone marrow-derived dendritic cells. In this study, we investigated the impact of Thy-1 signaling on the production of the T helper (Th) cell subset-associated cytokines, interferon (IFN) γ, interleukin (IL)-4 and IL-17, as well as the in vitro polarization of highly purified resting CD4+ T cells into Th1, Th2, and Th17 cells. Although CD8+ T cells expressed more Thy-1 than CD4+ T cells, both T cell populations were equally responsive to Thy-1 stimulation. In contrast to TcR signaling, which favored IFNγ production, Thy-1 signaling favored IL-17 synthesis and, to a lesser extent, IL-4 production, indicating a previously unidentified difference between the consequences of Thy-1 and TcR signal transduction. Moreover, Thy-1 signaling preferentially induced the Th17-associated transcription factor RORγt in CD4+ T cells. As with TcR signaling, Thy-1 stimulation of CD4+ T cells under the appropriate polarizing conditions resulted in Th1, Th2 or Th17 cell induction and cytokine synthesis that was maintained upon restimulation via Thy-1 or TcR crosslinking. The ability to provide a TcR-like signal capable of promoting T helper cell differentiation and cytokine synthesis was not common to all GPI-APs since cross-linking of Ly6A/E with mitogenic mAb did not promote substantial production of IFNγ, IL-4 or IL-17, although there was a substantial proliferative response. The preferential induction of Th2 and Th17 cytokine synthesis as a consequence of Thy-1 signaling suggests a default T helper cell response that may enhance host defense against extracellular pathogens.

Keywords: CD90, Cytokine synthesis, Glycosylphosphatidylinositol-anchored protein, T cell, Thy-1

Received: 15 Aug 2018; Accepted: 05 Nov 2018.

Edited by:

Lisette Leyton, Instituto de Ciencias Biomédicas, Universidad de Chile, Chile

Reviewed by:

Ivan L. Dzhagalov, National Yang-Ming University, Taiwan
David Lutz, Abteilung für Neuroanatomie und Molekulare Hirnforschung, Ruhr-Universität Bochum, Germany  

Copyright: © 2018 Hoskin, Furlong and Coombs. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. David Hoskin, Dalhousie University, Halifax, Canada, d.w.hoskin@dal.ca