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Frontiers in genetics
2020;11 610682.

Single-Cell RNA Sequencing of Tocilizumab-Treated Peripheral Blood Mononuclear Cells as an Model of Inflammation.

Arya Zarinsefat, George Hartoularos, Dmitry Rychkov, Priyanka Rashmi, Sindhu Chandran, Flavio Vincenti, Chun J Yee, Minnie M Sarwal
Author Information
  1. Arya Zarinsefat: Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
  2. George Hartoularos: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States.
  3. Dmitry Rychkov: Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
  4. Priyanka Rashmi: Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
  5. Sindhu Chandran: Department of Medicine, University of California, San Francisco, San Francisco, CA, United States.
  6. Flavio Vincenti: Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
  7. Chun J Yee: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, United States.
  8. Minnie M Sarwal: Department of Surgery, University of California, San Francisco, San Francisco, CA, United States.
PMID: 33469465 DOI: 10.3389/fgene.2020.610682

Abstract

COVID-19 has posed a significant threat to global health. Early data has revealed that IL-6, a key regulatory cytokine, plays an important role in the cytokine storm of COVID-19. Multiple trials are therefore looking at the effects of Tocilizumab, an IL-6 receptor antibody that inhibits IL-6 activity, on treatment of COVID-19, with promising findings. As part of a clinical trial looking at the effects of Tocilizumab treatment on kidney transplant recipients with subclinical rejection, we performed single-cell RNA sequencing of comparing stimulated PBMCs before and after Tocilizumab treatment. We leveraged this data to create an cytokine storm model, to better understand the effects of Tocilizumab in the presence of inflammation. Tocilizumab-treated cells had reduced expression of inflammatory-mediated genes and biologic pathways, particularly amongst monocytes. These results support the hypothesis that Tocilizumab may hinder the cytokine storm of COVID-19, through a demonstration of biologic impact at the single-cell level.

Keywords

COVID-19 bioinformatics and computational biology kidney transplantation single cell RNA seq tocilizumab (IL-6 inhibitor) transcriptomics

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Grants

  1. MR/L023784/1/Medical Research Council
  2. U19 AI128913/NIAID NIH HHS
  3. U01 AI113362/NIAID NIH HHS
  4. T32 AI125222/NIAID NIH HHS
  5. R01 DK109720/NIDDK NIH HHS
Journal Article

Links to CNCB-NGDC Resources

GEN: GEND000423 (Single-cell RNA sequencing of Tocilizumab-treated peripheral blood mononuclear cells as an in vitro model of inflammation)

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