ESPEYB20 8. Type 1 Diabetes New Hopes (3 abstracts)
8.16. Engineering the lymph node environment promotes antigen-specific efficacy in type 1 diabetes and islet transplantation
Gammon JM , Carey ST , Saxena V , Eppler HB , Tsai SJ , Paluskievicz C , Xiong Y , Li L , Ackun-Farmmer M , Tostanoski LH , Gosselin EA , Yanes AA , Zeng X , Oakes RS , Bromberg JS & Jewell CM
Nat Commun 2023;14(1):681.PMID: 36755035
Brief summary: In this experimental study, immunomodulatory microparticles, consisting of encapsulating self-antigens with rapamycin, were injected into mouse lymph nodes to protect against type 1 diabetes (T1D) and islet graft rejection. Antigens and rapamycin were both required for maximal efficacy and they induced durable tolerance, accompanied by expansion of antigen-specific regulatory T cells (Treg) in both treated and untreated lymph nodes.
Antigen-specific tolerance is a promising approach to prevent autoimmune diseases and allograft rejections, and aims to overcome the complications of extensive immunosuppression (1). This approach involves vaccine-like treatments that deliver autoantigens together with regulatory immune components to redirect autoantigen-specific T cells toward populations with regulatory immune roles (2). Given the key role of lymph nodes in immune responses, targeting this immune tissue with antigen-specific therapy appears an ideal approach.
These authors performed a series of experiments using pre-clinical models of CD4- and CD8-mediated T1D, and an allogenic islet transplant model in which full MHC mismatched donor islets were transferred to recipients after islet depletion. Direct lymph node injection of microparticles containing rapamycin (an immunomodulator) and islet autoantigens or allo-antigens were able to prevent T1D and islet graft rejection. Key results of this approach were that the microparticles induced a systemic antigen-tolerance with expansion in Treg in both treated and untreated lymph nodes. It also led to the development of tolerogenic structural microdomains in lymph nodes promoting memory markers among antigen-specific Tregs. Of note, there were no systemic immunosuppressive effects.
Altogether these data suggest a new model to promote long-lasting and selective tolerance in the context of T1D, with reduced or even absent side effects since it does not require any systemic or peripheral delivery. This model could also be translated to other autoimmune diseases and to prevent allograft rejection.
References: 1. Serra P, Santamaria P. Antigen-specific therapeutic approaches for autoimmunity. Nat Biotechnol. 2019;37(3):238–251. 2. Rose Lukesh N, Middleton DD, Bachelder EM, Ainslie KM. Particle-Based therapies for antigen specific treatment of type 1 diabetes. Int J Pharm. 2023;631:122500.
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ESPE Yearbook of Paediatric Endocrinology
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