Abstract:Background: Regulatory T cells (Tregs) are known to protect against allergies.Moreover, the decrease in the frequency and efficiency of Tregs amplifies allergic symptoms.Aim: This study investigated whether expanding Tregs in vivo with an IL-2/IL-2 antibody complex could be safe, well tolerated and efficient in a therapeutic setting in allergies.
Methods:We produced an anti-IL-2 antibody (1C6) and demonstrated that when it is complexed to human IL-2, it increases IL-2 efficiency to induce Tregs in vivo without… Show more
“…In both models, the suppressive function of Treg could further be enhanced by the CD4-binding HIV-1 surface protein gp120, preventing GvHD or allergic airway inflammation, respectively (79,80). Recently, it has been reported that low-dose IL-2 or a combination of IL-2/anti-IL-2 restored Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms (81)(82)(83). Manipulation of the intestinal microbiota associated with induction or expansion of Treg cells as shown in numerous animal models of allergy and asthma may also offer novel strategies for immunomodulation of food allergies.…”
Section: Current Therapeutic Applications In Allergic Diseases: I Ind...mentioning
Over the past decades, atopic diseases, including allergic rhinitis, asthma, atopic dermatitis, and food allergy, increased strongly worldwide, reaching up to 50% in industrialized countries. These diseases are characterized by a dominating type 2 immune response and reduced numbers of allergen-specific regulatory T (Treg) cells. Conventional allergen-specific immunotherapy is able to tip the balance towards immunoregulation. However, in mouse models of allergy adaptive transfer of Treg cells did not always lead to convincing beneficial results, partially because of limited stability of their regulatory phenotype activity. Besides genetic predisposition, it has become evident that environmental factors like a westernized lifestyle linked to modern sanitized living, the early use of antibiotics, and the consumption of unhealthy foods leads to epithelial barrier defects and dysbiotic microbiota, thereby preventing immune tolerance and favoring the development of allergic diseases. Epigenetic modification of Treg cells has been described as one important mechanism in this context. In this review, we summarize how environmental factors affect the number and function of Treg cells in allergic inflammation and how this knowledge can be exploited in future allergy prevention strategies as well as novel therapeutic approaches.
“…In both models, the suppressive function of Treg could further be enhanced by the CD4-binding HIV-1 surface protein gp120, preventing GvHD or allergic airway inflammation, respectively (79,80). Recently, it has been reported that low-dose IL-2 or a combination of IL-2/anti-IL-2 restored Treg numbers and function in respiratory and food allergies, thereby improving allergic markers and symptoms (81)(82)(83). Manipulation of the intestinal microbiota associated with induction or expansion of Treg cells as shown in numerous animal models of allergy and asthma may also offer novel strategies for immunomodulation of food allergies.…”
Section: Current Therapeutic Applications In Allergic Diseases: I Ind...mentioning
Over the past decades, atopic diseases, including allergic rhinitis, asthma, atopic dermatitis, and food allergy, increased strongly worldwide, reaching up to 50% in industrialized countries. These diseases are characterized by a dominating type 2 immune response and reduced numbers of allergen-specific regulatory T (Treg) cells. Conventional allergen-specific immunotherapy is able to tip the balance towards immunoregulation. However, in mouse models of allergy adaptive transfer of Treg cells did not always lead to convincing beneficial results, partially because of limited stability of their regulatory phenotype activity. Besides genetic predisposition, it has become evident that environmental factors like a westernized lifestyle linked to modern sanitized living, the early use of antibiotics, and the consumption of unhealthy foods leads to epithelial barrier defects and dysbiotic microbiota, thereby preventing immune tolerance and favoring the development of allergic diseases. Epigenetic modification of Treg cells has been described as one important mechanism in this context. In this review, we summarize how environmental factors affect the number and function of Treg cells in allergic inflammation and how this knowledge can be exploited in future allergy prevention strategies as well as novel therapeutic approaches.
“…1 ). In preclinical models, IL-2C-expanded Tregs not only protected from experimental autoimmune encephalitis and prolonged survival of allogeneic islet grafts [ 45 ] but also ameliorated allergen-induced airway hyperreactivity in prophylactic and therapeutic settings, where they reduced allergen-specific IgE serum levels [ 46 , 47 ] and expanded Treg during sublingual immunotherapy [ 48 ] and food allergy, respectively [ 49 ]. Moreover, it was shown that IL-2C-expanded Treg cells could be recalled upon allergen challenge, which was associated with suppression of lung-specific Th2 responses long after initial treatment [ 50 ].…”
Section: Distinct Monoclonal Antibodies Shape the Function And Increa...mentioning
Interleukin(IL)-2 was originally characterized as an important T-cellular growth factor but later on, turned out to be a pivotal homeostatic factor for the establishment and maintenance of both natural(n)Treg and peripheral(p)Treg. In this review, it was aimed to connect the peculiar structural and functional aspects of IL-2 to the innovative advancements in tailoring its multifaceted functional behavior for targeting various IL-2 receptor types. The article includes detailed descriptions of modified versions of IL-2, obtained by either mutating or fusing IL-2 to heterologous molecules or by forming IL-2/(monoclonal) antibody complexes (IL-2C), and discusses their functional implications for addressing such heterologous pathological conditions in cancer, autoimmunity, and allergy. Additionally, this review sheds light on the underexplored contribution of autoantibodies to the endogenous regulation of IL-2 within the realms of both health and disease. The ongoing efforts to fine-tune IL-2 responses through antibody-dependent targeting or molecular engineering offer considerable translational potential for the future utility of this important cytokine.
“…Treg cells are a subtype of T cells that maintain immune function and regulate immune adaptation. [177][178][179][180] The expression of Treg cells is closely related to the pathological state of the respiratory tract, and its functional impairment can potentially lead to autoimmune diseases. The increase of HIF-1α and HIF-2α in hypoxic conditions can inhibit the differentiation of Treg cells.…”
Chronic rhinosinusitis (CRS) is characterized by inflammation of the nasal cavity and the paranasal sinuses. [1][2][3][4] It has a significant impact on living and working conditions, affecting about 5%-12% of the general population. [5][6][7] Common complaints of such patients include nasal congestion, nasal discharge, altered sense of smell, facial pain, and facial pressure. The United States conservatively estimates that spending on CRS amounts up to $30 billion each year, inevitably creating a huge economic burden on society. 7 From an etiological point of view, CRS can be classified into primary and secondary forms. 8 Primary CRS is characterized by chronic inflammation of the nasal cavity and paranasal sinuses, where an obvious secondary causative factor is absent. Secondary
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