Tu9 - IL-6 Targeted Therapies Directed to Cytokine or Cytokine Receptor Blockade Drive Distinct Alterations in T Cell Function.

Tuesday, June 21, 2022

6:15 PM – 7:45 PM PT

Presenting Author(s)

Cate Speake, PhD

Research Assistant Member
Benaroya Research Institute
Seattle, Washington, United States

Co-Author(s)

TH

Tania Habib, PhD

Benaroya Research Institute
Seattle, Washington, United States
Katharina Lambert, PhD

Postdoctoral Researcher
Benaroya Research Institute
Seattle, Washington, United States
CH

Christian Hundhausen, PhD

Heinrich-Heine-University Dusseldorf
Dusseldorf, Nordrhein-Westfalen, Germany
SL

Sandra Lord, MD

Benaroya Research Institute
Seattle, Washington, United States
MD

Matthew Dufort, PhD

Benaroya Research Institute
Seattle, Washington, United States
SS

Samuel Skinner, PhD

Benaroya Research Institute
Seattle, Washington, United States
AH

Alex Hu, PhD

Benaroya Research Institute
Seattle, Washington, United States
MK

MacKenzie Kinsman, n/a

Benaroya Research Institute
Seattle, Washington, United States
BJ

Britta E. Jones, PhD

Postdoctoral Fellow
Benaroya Research Institute
Seattle, Washington, United States
MM

Megan Maerz, n/a

Benaroya Research Institute
Seattle, Washington, United States
MT

Megan Tatum, n/a

Benaroya Research Institute
Seattle, Washington, United States
Anne Hocking, PhD

Translational Research Program
Benaroya Research Institute
Seattle, Washington, United States
KC

Karen Cerosaletti, PhD

Benaroya Research Institute
Seattle, Washington, United States
Gerald T. Nepom, MD PhD

Director
Benaroya Research Institute / Immune Tolerance Network
Seattle, Washington, United States
CG

Carla Greenbaum, MD

Benaroya Research Institute
Seattle, Washington, United States
Jane H. Buckner, MD

President, BRI
Benaroya Research Institute
Seattle, Washington, United States

Multiple therapeutics that inhibit IL-6 at different points in the signaling pathway are in clinical use yet whether the immunologic effects of these interventions differ based on their molecular target is unknown. We performed short term interventions in individuals with type 1 diabetes using anti-IL-6 (siltuximab) or anti-IL-6 receptor (IL-6R; tocilizumab) and investigated the impact of this in vivo blockade on T cell fate and function. Immune outcomes were influenced by the target of the therapeutic intervention (IL-6 versus IL-6R) and by peak drug concentration. Tocilizumab but not siltuximab reduced IL-6 driven STAT3 phosphorylation, ICOS expression on T follicular helper cell populations and TCR driven STAT3 phosphorylation (TCR/pSTAT3). Siltuximab on the other hand, uniquely reversed resistance to Treg mediated suppression and increased TCR/pSTAT3, and IL-10, 21 and 27 production in T effectors. Together these findings indicate that the context of IL-6 blockade drives distinct T cell intrinsic changes that alter function.