Presenting Author: Chieh-Ying Kuo
, postdoctoral fellow at Chang Gung Univ., Chang Gung Univ.
Abstract:
It has been well established that cytokines produced by T helper 2 (Th2) cells are responsible for asthmatic pathogenesis. Thus, the blockade of co-stimulatory molecules may control Th2-cell activation and attenuate asthmatic responses. We firstly identified Cyn-1324, a small compound, with high binding affinity to CD28 and can disrupt the interaction between CD28/CD80. This study investigated whether Cyn-1324 serves as an immunomodulator via blocking CD28/CD80 signaling, leading to the interference of CD4+ T cell activations and the relief of allergic asthma. Among house dust mite (HDM)-induced asthmatic mice model, the intranasal administration of Cyn-1324 significantly reduced airway resistance, eosinophilia in lung, and Th2-associated cytokines production in antigen-stimulated lymphocytes culture supernatants. Furthermore, we further studied the immunosuppression effect of Cyn-1324 in vitro. Cyn-1324 decreased not only murine but also human T-cell proliferation and IL-2 secretion, through the induction of T-cell anergy. This is the first identified compound that directly binds to CD28 and leads to T-cell anergy, but not the induction of Tregs. In addition, these findings suggest the potential of Cyn-1324 as an immunosuppressive agent capable of attenuating allergic responses through the blockade of the CD28/CD80 interaction. Cyn-1324 emerges as a promising candidate for further exploration in developing immunosuppressive therapies for allergic or autoimmune diseases.
A Novel CD28-Targeting Molecule with Potent Therapeutic Impact on Asthma
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1