A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Helper T Cell (CD4(+)) Targeted Tacrolimus Delivery Mediates Precise Suppression of Allogeneic Humoral Immunity
Tekijät: Shen Jia, Liu Chang, Yan Pengpeng, Wang Meifang, Guo Luying, Liu Shuaihui, Chen Jianghua, Rosenholm Jessica M, Huang Hongfeng, Wang Rending, Zhang Hongbo
Kustantaja: AMER ASSOC ADVANCEMENT SCIENCE
Julkaisuvuosi: 2022
Journal: Research
Tietokannassa oleva lehden nimi: RESEARCH
Lehden akronyymi: RESEARCH-CHINA
Artikkelin numero: 9794235
Vuosikerta: 2022
Sivujen määrä: 15
ISSN: 2096-5168
eISSN: 2639-5274
DOI: https://doi.org/10.34133/2022/9794235
Verkko-osoite: https://spj.sciencemag.org/journals/research/2022/9794235/
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/176160307
Antibody-mediated rejection (ABMR) is a major cause of dysfunction and loss of transplanted kidney. The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells. However, the prognosis of patients following current treatment is poor. T follicular helper cells (Tfh) play an important role in allograft-specific antibodies secreting plasma cell (PC) development. Tfh cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders, such as transplant rejection and autoimmune diseases. Tacrolimus (Tac), the primary immunosuppressant, prevents rejection by reducing T cell activation. However, its administration should be closely monitored to avoid serious side effects. In this study, we investigated whether Tac delivery to helper T (CD4(+)) cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen exposure. Results showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development, PC, and donor-specific antibody (DSA) generation without causing severe side effects compared with delivery through the drug administration pathway. This study provides a promising therapeutic strategy for preventing humoral rejection in solid organ transplantation. The specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.
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