IL-6 and IL-27 play both distinct and redundant roles in regulating CD4 T-cell responses during chronic viral infection

Front Immunol. 2023 Jul 31:14:1221562. doi: 10.3389/fimmu.2023.1221562. eCollection 2023.

Abstract

The IL-6 cytokine family signals through the common signal transduction molecule gp130 combined with a cytokine-specific receptor. Gp130 signaling on CD4 T cells is vital in controlling chronic infection of mice with lymphocytic choriomeningitis virus clone 13 (LCMV Cl13), but the precise role of individual members of the IL-6 cytokine family is not fully understood. Transcriptional analysis highlighted the importance of gp130 signaling in promoting key processes in CD4 T cells after LCMV Cl13 infection, particularly genes associated with T follicular helper (Tfh) cell differentiation and IL-21 production. Further, Il27r-/-Il6ra-/- mice failed to generate antibody or CD8 T-cell immunity and to control LCMV Cl13. Transcriptomics and phenotypic analyses of Il27r-/-Il6ra-/- Tfh cells revealed that IL-6R and IL-27R signaling was required to activate key pathways within CD4 T cells. IL-6 and IL-27 signaling has distinct and overlapping roles, with IL-6 regulating Tfh differentiation, IL-27 regulating CD4 T cell survival, and both redundantly promoting IL-21.

Keywords: IL-27; IL-6; T follicular helper cells; chronic viral infection; lcmv.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • Cytokine Receptor gp130 / genetics
  • Cytokine Receptor gp130 / metabolism
  • Interleukin-27* / metabolism
  • Interleukin-6 / metabolism
  • Lymphocytic Choriomeningitis*
  • Lymphocytic choriomeningitis virus
  • Mice
  • Persistent Infection
  • Receptors, Cytokine / genetics

Substances

  • Interleukin-27
  • Interleukin-6
  • Cytokine Receptor gp130
  • Receptors, Cytokine