Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β

Abstract

The prevalence of allergic diseases has significantly increased in industrialized countries. Allergen-specific immunotherapy (AIT) remains as the only curative treatment. The knowledge about the mechanisms underlying healthy immune responses to allergens, the development of allergic reactions and restoration of appropriate immune responses to allergens has significantly improved over the last decades. It is now well-accepted that the generation and maintenance of functional allergen-specific regulatory T (Treg) cells and regulatory B (Breg) cells are essential for healthy immune responses to environmental proteins and successful AIT. Treg cells comprise different subsets of T cells with suppressive capacity, which control the development and maintenance of allergic diseases by various ways of action. Molecular mechanisms of generation of Treg cells, the identification of novel immunological organs, where this might occur in vivo, such as tonsils, and related epigenetic mechanisms are starting to be deciphered. The key role played by the suppressor cytokines interleukin (IL)-10 and transforming growth factor (TGF)-β produced by functional Treg cells during the generation of immune tolerance to allergens is now well established. Treg and Breg cells together have a role in suppression of IgE and induction of IgG4 isotype allergen-specific antibodies particularly mediated by IL-10. Other cell types such as subsets of dendritic cells, NK-T cells and natural killer cells producing high levels of IL-10 may also contribute to the generation of healthy immune responses to allergens. In conclusion, better understanding of the immune regulatory mechanisms operating at different stages of allergic diseases will significantly help the development of better diagnostic and predictive biomarkers and therapeutic interventions.

MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88

“…Depending on the encountered antigens and surrounding environment, DCs can integrate different signaling pathways and polarize distinct effector Th or regulatory T (Treg) cells using a wide battery of soluble and membrane-bound factors. [26][27][28][29][30] This function is of paramount importance to protect the organism against potentially dangerous pathogens while keeping homeostasis and tolerance to innocuous and self-antigens. 29,[31][32][33] MV140-induced Th1 and Th17 cells could contribute to clear intracellular and extracellular pathogens whereas the IL-10-producing T cells could control excessive immune responses, avoid deleterious consequences for the tissues and contribute to pathogen clearance by keeping homeostasis.…”

“…[26][27][28][29][30] This function is of paramount importance to protect the organism against potentially dangerous pathogens while keeping homeostasis and tolerance to innocuous and self-antigens. 29,[31][32][33] MV140-induced Th1 and Th17 cells could contribute to clear intracellular and extracellular pathogens whereas the IL-10-producing T cells could control excessive immune responses, avoid deleterious consequences for the tissues and contribute to pathogen clearance by keeping homeostasis. [34][35][36] Our data suggest that the generated IL-10-producing T cells could phenotypically correspond to induced type 1 regulatory T cells (Treg1).…”

Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease

“…The mechanism behind this tolerance induction is based on the generation or expansion of antigen-specific CD4+CD25+FoxP3+ T-cells (T regs ) after hepatic gene transfer that dampen systemic responses through cell contact-and cytokine-dependent pathways. [26][27][28][29][30] The systemic pathology associated with Pompe disease may not benefit from long-term liver-restricted expression as any GAA produced into the circulation would mimic ERT and therefore face the same limitations related to inadequate uptake into neuronal tissues. 31 Targeting of the liver to induce immune tolerance to GAA has, however, demonstrated some success, but further development of a safe and efficient means to establish systemic correction with accompanying tolerance is warranted.…”

Neurturin Influences Inflammatory Responses and Airway Remodeling in Different Mouse Asthma Models

“…However, the effect of TGF-b1 in asthma diseases is diverse. Thus, this cytokine can have promoting effects, because when expressed by airway epithelial cells, it participates to the remodeling and fibrosis in asthmatic patients (12)(13)(14). On its side, the secreted NTN preferentially activates a pathway via a GPIlinked receptor termed GDNF family receptor a-2 (GFRa-2) and the tyrosine kinase RET (15).…”