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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01553

14-3-3zeta - A Novel Immunogen Promotes Inflammatory Cytokine Production

  • 1College of Medicine and Life Sciences, University of Toledo, United States
  • 2University of Toledo, United States

The presence of autoantibodies against 14-3-3z in human autoimmune diseases indicates its antigenic function. However, neither the cause nor the consequence of this newly-identified antigenic function of 14-3-3z protein is known. To address this, we investigated the immunological functions of 14-3-3z by studying ex vivo effects on human peripheral blood mononuclear cells (PBMC) proliferation, polarization and cytokine production. Exogenous 14-3-3z promoted PBMC proliferation and T cell polarization towards increasing Th1 and Th17 populations. Significant increases in IFN-g and IL-17 levels were observed in the presence of 14-3-3z. A specific increase in Th1 cells and IFN-g production provided strong evidence for MHC class II presentation of 14-3-3z antigen. Particularly HLA-DRB1*0401 allele strongly promoted 14-3-3z-induced IFN-g producing cells. In contrast, prednisolone treatment inhibited 14-3-3z-induced both T cell polarization and cytokine production. Overall, we show that MHC presentation and adaptor functions of 14-3-3z participate in promoting IFN-g and IL-17 production, two of the cytokines commonly associated with autoimmune diseases. To the best of our knowledge, this is the first report describing the ex vivo antigenic function of 14-3-3z with human PBMC, thereby providing the basis of its immunological role in human diseases.

Keywords: 14-3-3zeta, autoantigen, T cell polarization, Interferon-gamma, IL-17, HLA-DRB1

Received: 28 Feb 2019; Accepted: 21 Jun 2019.

Edited by:

Jagadeesh BAYRY, Institut National de la Santé et de la Recherche Médicale (INSERM), France

Reviewed by:

Kevin J. Marchbank, Newcastle University, United Kingdom
Halmuthur M. SampathKumar, Indian Institute of Chemical Technology (CSIR), India  

Copyright: © 2019 Chakravarti, Chattopadhyay, McGowan and peter. 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: Dr. Ritu Chakravarti, College of Medicine and Life Sciences, University of Toledo, Toledo, 43606, Ohio, United States, ritu.chakravarti@utoledo.edu