Emerging Insights in Controlling Autoimmunity

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Background

Autoimmunity and autoimmune diseases evolve when mechanisms of self-tolerance fail, allowing the expansion of auto-reactive B and T lymphocytes, and the continuous secretion of pro-inflammatory cytokines. For many years our main attention was directed towards a better understanding of the complexity of both humoral and cellular responses in autoimmunity. Specifically, the role of autoantibodies, and Th1\Th17 or Th2 related pro-inflammatory cytokines in different autoimmune diseases. This was subsequently followed by the development of anti-inflammatory therapies, largely aimed at blocking these cytokines with relevant monoclonal antibodies. Without neglecting the role of pro-inflammatory responses in the pathogenesis of autoimmune diseases, there has recently been an increased focus on assessing the importance of the regulatory system, the main function of which is to maintain self-tolerance and prevent the development of autoimmune diseases.

Initially, T regulatory cells (Tregs, comprising 10% of all CD4+ T cells) were considered to be the only regulatory cells, the role of which is to prevent the expansion of auto-reactive T and B lymphocytes, natural killer cells and dendritic cells. This is achieved by the ability of these cells, upon specific activation, to secrete inhibitory cytokines, such as IL-10, TGF-β and IL-35. The expression of the inhibitory molecule, CTLA-4, on Tregs allows a cell-to-cell way of regulation, by down-regulating co-stimulatory molecules on effector T lymphocytes and dendritic cells. More recently, B regulatory cells (Bregs) have also been indicated as an important feature of regulatory mechanisms. Bregs have no specific transcription factor (such as FoxP3) or specific membrane molecules identified. However, they do secrete inhibitory cytokines such as IL-10 and IL-35 in a specific antigen-dependent way and they also secrete blocking IgG4 (which plays a role in preventing allergic diseases). Additional regulatory molecules, such as semaphorin3A, have also been implicated in maintaining self-tolerance and as therapeutic candidates for the prevention of lupus nephritis and bronchial asthma.

In this Research Topic, we call for all articles - including studies on animal models - that are related to the role of regulatory cells/molecules, in different autoimmune diseases and their possible role in the treatment of these diseases. This includes, but is not limited to:

• New insights on T and B regulatory cells – mode of action, how they affect status of IL-23/IL-17, the expression of CD5 or CD6 on effector T cells
• IgG4 in preventing allergic diseases, their role in assessing the success of allergen immunotherapy
• Innovations in the understanding of how semaphoring3A restores self-tolerance and prevents inflammatory processes
• Failure of regulatory mechanisms in preventing the development of graft-vs-host disease
• Potential therapeutic approaches that are related to regulatory molecules

Keywords: Controlling autoimmunity, regulatory molecules, inhibitory cytokines, IL-23, IL-17

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