Abstract
Abstract Increased levels of IL-17 and IL-23 have been associated with autoimmunity,but their effects on thymocyte selection have not been studied.To test this,normal B6 mice were injected with adenovirus expressing either IL-17 (AdIL17) or IL-23 (AdIL-23).There was dramatic reduction of thymus cellularity and increased apoptosis of DP thymocytes in AdIL-23 injected mice.Coinjection of AdIL-17 potentiated the effects of AdIL-23.Coinjection of anti-IL-17 antibody with AdIL-23 partially corrected the effects of AdIL-23 to deplete DP thymocytes by blocking IL-17 induced recruitment of CD11b+ and CD11c+ cells in the junction between cortex and medulla where they exhibit the maximal interaction with DP thymocytes.AdIL-23 but not AdIL-17 or AdLacZ treatment largely increased the expression of IL-23 receptor in DP thymocytes and further lead to 100 fold increased expression of RORgt which is an important DP thymocyte apoptosis inducing molecule.In vitro coculture of thymocytes from 2D2 TCR transgenic mice with MOG35-55 peptide pulsed dendritic cells showed that there were enhanced apoptosis and a lower proliferative response of thymocytes in the presence of IL-23 but not IL-17.Taken together,our results suggest that IL-17 acts to recruit antigen-presenting cells to interact with DP thymocytes,IL-23 induces deletion of Ag encountering DP thymocytes.Thus,interaction of these two cytokines limits the generation of self-reactive thymocytes and does not lead to autoimmunity in normal mice.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call