Regulatory T cells and immunoglobulin E: A new therapeutic link for autoimmunity?

Abstract

Autoimmune diseases have a prevalence of approximately 7 to 9% and are classified as either organ‐specific diseases, including type I diabetes, multiple sclerosis, inflammatory bowel disease and myasthenia gravis, or systemic diseases, including systemic lupus erythematosus, rheumatoid arthritis and Sjögren's syndrome. While many advancements have been made in understanding of the mechanisms of autoimmune disease, including the nature of self‐tolerance and its breakdown, there remain unmet needs in terms of effective and highly targeted treatments. T regulatory cells (Tregs) are key mediators of peripheral tolerance and are implicated in many autoimmune diseases, either as a result of reduced numbers or altered function. Tregs may be broadly divided into those generated in the thymus (tTregs) and those generated in the periphery (pTregs). Tregs target many different immune cell subsets and tissues to suppress excessive inflammation and to support tissue repair and homeostasis: there is a fine balance between Treg cell stability and the plasticity that is required to adjust Tregs' regulatory purposes to particular immune responses. The central role of immunoglobulin E (IgE) in allergic disease is well recognized, and it is becoming increasingly apparent that this immunoglobulin also has a wider role encompassing other diseases including autoimmune disease. Anti‐IgE treatment restores the capacity of plasmacytoid dendritic cells (pDCs) impaired by IgE‐ high‐affinity IgE receptor (FcεR1) cross‐linking to induce Tregs in vitro in atopic patients. The finding that anti‐IgE therapy restores Treg cell homeostasis, and that this mechanism is associated with clinical improvement in asthma and chronic spontaneous urticaria suggests that anti‐IgE therapy may also have a potential role in the treatment of autoimmune diseases in which Tregs are involved.

Cannabinoid WIN55,212-2 reprograms monocytes and macrophages to inhibit LPS-induced inflammation

“…Likewise, WIN-hmoDCs primed FOXP3 + Tregs and displayed reduced capacity to polarize both Th1 and Th2 responses. The induction and/or expansion of Tregs is essential to keep homeostasis in the context of immune-mediated and inflammatory diseases (31)(32)(33), which might be regulated by exogenous signals including cannabinoids like cannabidiol (CBD), JTE907 or O-1966 (34)(35)(36). We previously showed that fully differentiated conventional hmoDCs and blood DCs subsets stimulated in vitro with toll-like receptor ligands in the presence of promote functional Tregs (13,37,38), which was further corroborated in vivo in LPS-induced sepsis, peanut-allergic sensitization and anaphylaxis models (13,37).…”

Vasoactive intestinal peptide exerts therapeutic action by regulating PTEN in a model of Sjögren's disease

“…Earlier studies have revealed an increase in the pathogenic Th17 cells in patients, which contribute to the pathogenesis of SS 11 . Since Treg cells are the main suppressors of the excessive activation of immune responses, the recent advances in the therapeutic strategy of SS are to target Treg homeostasis or its associated signaling pathway 34 . Here we found that PTEN knockdown decreased the Treg/Th17 ratio in SPLCs, and that VIP treatment increased the Treg/Th17 ratio and the expression of PTEN.…”

Systemic lupus erythematosus: latest insight into etiopathogenesis

“…Autoreactive IgE, such as anti-dsDNA IgE, was found to be elevated in SLE patients and can also elicit an increase in IFNα production by binding the Fc epsilon RI (FcεRI) of plasmacytoid dendritic cells (pDCs) [ 17 ]. The binding of IgE to pDCs also enhances the follicular T cell expansion and reduces the Treg population, which increased the inflammatory condition in lupus patients [ 18 ]. IFN-α can also activate the IL-1 receptor-associated kinase that further induces apoptosis in Treg cells from SLE patients [ 19 ].…”