Re-Programming Autoreactive T Cells Into T-Regulatory Type 1 Cells for the Treatment of Autoimmunity

Front Immunol. 2021 Jul 15:12:684240. doi: 10.3389/fimmu.2021.684240. eCollection 2021.


Systemic delivery of peptide-major histocompatibility complex (pMHC) class II-based nanomedicines can re-program cognate autoantigen-experienced CD4+ T cells into disease-suppressing T-regulatory type 1 (TR1)-like cells. In turn, these TR1-like cells trigger the formation of complex regulatory cell networks that can effectively suppress organ-specific autoimmunity without impairing normal immunity. In this review, we summarize our current understanding of the transcriptional, phenotypic and functional make up of TR1-like cells as described in the literature. The true identity and direct precursors of these cells remain unclear, in particular whether TR1-like cells comprise a single terminally-differentiated lymphocyte population with distinct transcriptional and epigenetic features, or a collection of phenotypically different subsets sharing key regulatory properties. We propose that detailed transcriptional and epigenetic characterization of homogeneous pools of TR1-like cells will unravel this conundrum.

Keywords: T-cell reprogramming; T-regulatory type 1 (TR1) cells; autoimmune disease; interleukin 10 (IL10); peptide-MHC class II-coated nanoparticles; therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoantigens / immunology
  • Autoimmunity*
  • Epigenomics
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Nanomedicine
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology


  • Autoantigens
  • Histocompatibility Antigens Class II

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