In:
Frontiers in Immunology, Frontiers Media SA, Vol. 12 ( 2022-1-4)
Abstract:
Changes in innate and adaptive immunity occurring in/around pancreatic islets had been observed in peripheral blood mononuclear cells (PBMC) of Caucasian T1D patients by some, but not all researchers. The aim of our study was to investigate whether gene expression patterns of PBMC of the highly admixed Brazilian population could add knowledge about T1D pathogenic mechanisms. Methods We assessed global gene expression in PBMC from two groups matched for age, sex and BMI: 20 patients with recent-onset T1D (≤ 6 months from diagnosis, in a time when the autoimmune process is still highly active), testing positive for one or more islet autoantibodies and 20 islet autoantibody-negative healthy controls. Results We identified 474 differentially expressed genes between groups. The most expressed genes in T1D group favored host defense, inflammatory and anti-bacterial/antiviral effects ( LFT, DEFA4, DEFA1, CTSG, KCNMA1 ) and cell cycle progression. Several of the downregulated genes in T1D target cellular repair, control of inflammation and immune tolerance. They were related to T helper 2 pathway, induction of FOXP3 expression ( AREG ) and immune tolerance ( SMAD6 ) . SMAD6 expression correlated negatively with islet ZnT8 antibody. The expression of PDE12 , that offers resistance to viral pathogens was decreased and negatively related to ZnT8A and GADA levels. The increased expression of long non coding RNAs MALAT1 and NEAT1, related to inflammatory mediators, autoimmune diseases and innate immune response against viral infections reinforced these data Conclusions Our analysis suggested the activation of cell development, anti-infectious and inflammatory pathways, indicating immune activation, whereas immune-regulatory pathways were downregulated in PBMC from recent-onset T1D patients with a differential genetic profile.
Type of Medium:
Online Resource
ISSN:
1664-3224
DOI:
10.3389/fimmu.2021.765264
DOI:
10.3389/fimmu.2021.765264.s001
DOI:
10.3389/fimmu.2021.765264.s002
DOI:
10.3389/fimmu.2021.765264.s003
DOI:
10.3389/fimmu.2021.765264.s004
DOI:
10.3389/fimmu.2021.765264.s005
DOI:
10.3389/fimmu.2021.765264.s006
DOI:
10.3389/fimmu.2021.765264.s007
DOI:
10.3389/fimmu.2021.765264.s008
DOI:
10.3389/fimmu.2021.765264.s009
DOI:
10.3389/fimmu.2021.765264.s010
DOI:
10.3389/fimmu.2021.765264.s011
DOI:
10.3389/fimmu.2021.765264.s012
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2606827-8
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