Research Topic

Generating and Sustaining Stable Autoantigen-specific CD4 and CD8 Regulatory T Cells in Lupus

About this Research Topic

Recently, several worldwide clinical and pre-clinical trials have demonstrated a significant benefit of low dose IL-2 mediated Treg cell increase in multiple autoimmune diseases, including lupus. This result is of special interest in lupus because it has been known for decades that during lupus the immune system has a relative deficiency of IL-2 production that results in a decrease in regulatory T cells and a simultaneous increase in T follicular helper (Tfh) cells. Thus, the low dose IL-2 therapy benefits lupus in several ways, but the effect is very short-lived, as the level of Treg comes down rapidly. Moreover, the Tregs generated by the therapy are non-specific and probably unstable, meaning that they could convert to pathogenic T cells in the inflammatory environment of lupus. The reason for this dilemma is that continuous T cell receptor signals are required to maintain a functional regulatory T cell pool, and effector Tregs are very potent only after rounds of antigen specific activation in low intensity. Therefore, autoantigen-derived peptide epitopes for T cells of lupus that have been proven to be tolerance-inducing in low-doses because they generate autoantigen-specific CD4 and CD8 regulatory T cells, are crucial for generating and sustaining stable Treg. Moreover, the subset of regulatory CD8 T cells induced by some of the peptide epitopes are especially beneficial in human lupus. The autoantigen peptide epitopes, however, may require special delivery system involving nanoparticles and adjunct therapy with anti-inflammatory agents to secure their durable tolerogenicity in lupus patient. Thus, this Research Topic invites contributions from experts related to, but not limited to, the following categories:

1) Lupus T cell epitopes with known Treg inducing ability/tolerogenicity;
2) Tolerogenic delivery of epitopes, such as in nanoparticles;
3) Treg stability maintenance mechanisms, such as molecular and epigenetic mechanisms, metabolic mechanisms;
4) Potentiate peptide tolerance by IL-2 and other adjunct therapy such as IL-2 in low dose, or in nanoparticles, IL-2 muteins, or pegylated IL-2, and other agents.

David Horwitz has co-founded Toralgen, INC and General Nanotherapeutics, LLC but is receiving no compensation for either company. All other Topic Editors declare no conflicts of interest related to the topic theme


Keywords: lupus autoimmunity, lupus T cell epitopes, tolerogenic delivery, Stable Treg molecular mechanism, potentiate peptide tolerance


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Recently, several worldwide clinical and pre-clinical trials have demonstrated a significant benefit of low dose IL-2 mediated Treg cell increase in multiple autoimmune diseases, including lupus. This result is of special interest in lupus because it has been known for decades that during lupus the immune system has a relative deficiency of IL-2 production that results in a decrease in regulatory T cells and a simultaneous increase in T follicular helper (Tfh) cells. Thus, the low dose IL-2 therapy benefits lupus in several ways, but the effect is very short-lived, as the level of Treg comes down rapidly. Moreover, the Tregs generated by the therapy are non-specific and probably unstable, meaning that they could convert to pathogenic T cells in the inflammatory environment of lupus. The reason for this dilemma is that continuous T cell receptor signals are required to maintain a functional regulatory T cell pool, and effector Tregs are very potent only after rounds of antigen specific activation in low intensity. Therefore, autoantigen-derived peptide epitopes for T cells of lupus that have been proven to be tolerance-inducing in low-doses because they generate autoantigen-specific CD4 and CD8 regulatory T cells, are crucial for generating and sustaining stable Treg. Moreover, the subset of regulatory CD8 T cells induced by some of the peptide epitopes are especially beneficial in human lupus. The autoantigen peptide epitopes, however, may require special delivery system involving nanoparticles and adjunct therapy with anti-inflammatory agents to secure their durable tolerogenicity in lupus patient. Thus, this Research Topic invites contributions from experts related to, but not limited to, the following categories:

1) Lupus T cell epitopes with known Treg inducing ability/tolerogenicity;
2) Tolerogenic delivery of epitopes, such as in nanoparticles;
3) Treg stability maintenance mechanisms, such as molecular and epigenetic mechanisms, metabolic mechanisms;
4) Potentiate peptide tolerance by IL-2 and other adjunct therapy such as IL-2 in low dose, or in nanoparticles, IL-2 muteins, or pegylated IL-2, and other agents.

David Horwitz has co-founded Toralgen, INC and General Nanotherapeutics, LLC but is receiving no compensation for either company. All other Topic Editors declare no conflicts of interest related to the topic theme


Keywords: lupus autoimmunity, lupus T cell epitopes, tolerogenic delivery, Stable Treg molecular mechanism, potentiate peptide tolerance


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 August 2020 Abstract
30 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 August 2020 Abstract
30 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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