Thy-1 (CD90) Signaling Preferentially Promotes RORγt Expression and a Th17 Response

• Main Authors: Suzanne Furlong, Melanie R. Power Coombs, Javad Ghassemi-Rad, David W. Hoskin
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-11-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: CD90; cytokine synthesis; glycosylphosphatidylinositol-anchored protein; T cell; Thy-1
• Online Access: https://www.frontiersin.org/article/10.3389/fcell.2018.00158/full

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-17A, 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 stimulation of CD3+ T cells, which favored IFNγ and IL-4 production, Thy-1 signaling favored IL-17 synthesis, 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; however, Thy-1 stimulation induced nearly 7- and 2-fold more IL-4 and IL-17A, respectively, but only slightly more IFNγ. 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 RORγt 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.