Immunoregulatory Biomarkers of the Remission Phase in Type 1 Diabetes : miR-30d-5p Modulates PD-1 Expression and Regulatory T Cell Expansion
Gómez Muñoz, Laia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Perna-Barrull, David (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Murillo-Vallés, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Armengol, Maria Pilar (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Alcalde, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Català, Martí (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Rodríguez-Fernández, Silvia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sunye, Sergi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Valls, Aina (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pérez Sánchez, Jacobo (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Corripio, Raquel (Parc Taulí Hospital Universitari. Institut d'Investigació i Innovació Parc Taulí (I3PT))
Vives Pi, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	The partial remission (PR) phase of type 1 diabetes (T1D) is an underexplored period characterized by endogenous insulin production and downmodulated autoimmunity. To comprehend the mechanisms behind this transitory phase and develop precision medicine strategies, biomarker discovery and patient stratification are unmet needs. MicroRNAs (miRNAs) are small RNA molecules that negatively regulate gene expression and modulate several biological processes, functioning as biomarkers for many diseases. Here, we identify and validate a unique miRNA signature during PR in pediatric patients with T1D by employing small RNA sequencing and RT-qPCR. These miRNAs were mainly related to the immune system, metabolism, stress, and apoptosis pathways. The implication in autoimmunity of the most dysregulated miRNA, miR-30d-5p, was evaluated in vivo in the non-obese diabetic mouse. MiR-30d-5p inhibition resulted in increased regulatory T cell percentages in the pancreatic lymph nodes together with a higher expression of CD200. In the spleen, a decrease in PD-1 + T lymphocytes and reduced PDCD1 expression were observed. Moreover, miR-30d-5p inhibition led to an increased islet leukocytic infiltrate and changes in both effector and memory T lymphocytes. In conclusion, the miRNA signature found during PR shows new putative biomarkers and highlights the immunomodulatory role of miR-30d-5p, elucidating the processes driving this phase.
Grants:	Instituto de Salud Carlos III PI18/00436 Instituto de Salud Carlos III PI22/00045
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Biomarker ; Childhood ; Epigenetics ; Honeymoon ; Immune regulation ; Islet autoimmunity ; Microrna ; Partial remission ; Regulatory T cell ; Type 1 diabetes
Published in:	Non-Coding RNA, Vol. 9 (february 2023) , ISSN 2311-553X

DOI: 10.3390/ncrna9020017
PMID: 36960962

27 p, 6.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Parc Taulí Research and Innovation Institute (I3PT
Articles > Research articles
Articles > Published articles