1. Transcriptional re-programming of insulin B-chain epitope-specific T-follicular helper cells into anti-diabetogenic T-regulatory type-1 cells
- Author
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Patricia Solé, Daniel Parras, Jun Yamanouchi, Josep Garnica, Nahir Garabatos, Joel Moro, Javier Montaño, Debajyoti Mondal, César Fandos, Yang Yang, Pau Serra, and Pere Santamaria
- Subjects
peptide-major histocompatibility complex (pMHC) molecules ,nanomedicine ,antigen-specific tolerance ,immunoregulation ,T-regulatory type 1 (TR1) cells ,type 1 diabetes ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Systemic delivery of nanoparticles (NPs) coated with mono-specific autoimmune disease-relevant peptide-major histocompatibility complex class II (pMHCII) molecules can resolve organ inflammation in various disease models in a disease-specific manner without impairing normal immunity. These compounds invariably trigger the formation and systemic expansion of cognate pMHCII-specific T-regulatory type 1 (TR1) cells. By focusing on type 1 diabetes (T1D)-relevant pMHCII-NP types that display an epitope from the insulin B-chain bound to the same MHCII molecule (IAg7) on three different registers, we show that pMHCII-NP-induced TR1 cells invariably co-exist with cognate T-Follicular Helper (TFH)-like cells of quasi-identical clonotypic composition and are oligoclonal, yet transcriptionally homogeneous. Furthermore, these three different TR1 specificities have similar diabetes reversal properties in vivo despite being uniquely reactive against the peptide MHCII-binding register displayed on the NPs. Thus, pMHCII-NP treatment using nanomedicines displaying different epitope specificities results in the simultaneous differentiation of multiple antigen-specific TFH-like cell clones into TR1-like cells that inherit the fine antigenic specificity of their precursors while acquiring a defined transcriptional immunoregulatory program.
- Published
- 2023
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