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Central European Journal of Immunology
eISSN: 1644-4124
ISSN: 1426-3912
Central European Journal of Immunology
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1/2025
vol. 50
 
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abstract:
Original paper

Inhibition of miR-155 attenuates dendritic cell maturation and skin allograft rejection through SOCS1 in a rhesus monkey model

Qiuhong Wang
1
,
Bo Tang
1
,
Dong Wei
1
,
Dongyun Cun
1
,
Tao Wu
1
,
Renchao Zou
1
,
Tao Wang
1
,
Kun Su
1
,
Lianmin Wang
1
,
Peng Chen
1
,
Mingdao Hu
1

  1. Departments of Hepatopancreatobiliary Surgery, The Second Affiliated Hospital of Kunming Medical University, China
Cent Eur J Immunol 2025; 50 (1): 52-76
DOI: https://doi.org/10.5114/ceji.2025.149439
Online publish date: 2025/05/05
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Introduction:
Modulating dendritic cells (DCs; inhibiting maturation and antigen-presenting capacity) potentially promote immune tolerance to the benefit of allografts. In this study, we aimed to elucidate the impact of miR-155 on DC maturation and allograft rejection.

Material and methods:
Donor monkey bone marrow-derived dendritic cells (BMDCs) were transduced with anti-miR-155 lentivirus to inhibit miR-155 expression, and the T cell phenotype and function of DCanti-155 upon lipopolysaccharide (LPS) stimulation were evaluated. In vivo, imDC, imDCanti-NC, and imDCanti-155 were injected into recipient monkeys before skin transplantation. The survival times of skin allografts were recorded and the proportions of T cell subsets in spleen and secretion levels of cytokines in serum were measured. SOCS1/JAK/STAT pathway expression was also examined.

Results:
miR-155 level increased during the maturation of dendritic cells. Inhibition of miR-155 significantly attenuated LPS-induced DC maturation. imDCanti-155 promoted the differentiation of regulatory T cells (Tregs) and augmented the secretion of immunosuppressive cytokines. In vivo, subcutaneous injection of imDCanti-155 prolonged recipient monkey skin allograft survival times and attenuated immune rejection. An increase in the proportion of Treg cells and their secreted cytokines in serum was observed in the imDCanti-155 group. Mechanistic insights suggest that miR-155 likely regulates the SOCS1-JAK/STAT pathway.

Conclusions:
Suppression of miR-155 has the potential to inhibit DC maturation, affects the differentiation of T cell subsets, and prolongs skin allograft survival, which could serve as a promising therapeutic strategy for managing allograft rejection.

keywords:

immune tolerance, dendritic cell maturation, miR-155, Treg differentiation, anti-inflammatory cytokines
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