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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Alloimmunity and Transplantation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1407118
This article is part of the Research Topic The future direction toward immunological issues of allo-and xeno-islet transplantation View all 10 articles

Exploring the Molecular Mechanisms of Macrophages in Islet Transplantation Using Single-Cell Analysis

Provisionally accepted
  • 1 Shenzhen Second People’s Hospital, Shenzhen, China
  • 2 Shenzhen Second People's Hospital, Shenzhen, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Background Islet transplantation is a promising treatment for type 1 diabetes that aims to restore insulin production and improve glucose control, but long-term graft survival remains a challenge due to immune rejection.Methods ScRNA-seq data from syngeneic and allogeneic islet transplantation grafts were obtained from GSE198865. Seurat was used for filtering and clustering, and UMAP was used for dimension reduction. Differentially expressed genes were analyzed between syngeneic and allogeneic islet transplantation grafts. Gene set variation analysis (GSVA) was performed on the HALLMARK gene sets from MSigDB. Monocle 2 was used to reconstruct differentiation trajectories, and cytokine signature enrichment analysis was used to compare cytokine responses between syngeneic and allogeneic grafts.Three distinct macrophage clusters (Mø-C1, Mø-C2, and Mø-C3) were identified, revealing complex interactions and regulatory mechanisms within macrophage populations. The significant activation of macrophages in allogeneic transplants was marked by the upregulation of allograft rejection-related genes and pathways involved in inflammatory and interferon responses. GSVA revealed eight pathways significantly upregulated in the Mø-C2 cluster. Trajectory analysis revealed that Mø-C3 serves as a common progenitor, branching into Mø-C1 and Mø-C2. Cytokine signature enrichment analysis revealed significant differences in cytokine responses, highlighting the distinct immunological environments created by syngeneic and allogeneic grafts.This study significantly advances the understanding of macrophage roles within the context of islet transplantation by revealing the interactions between immune pathways and cellular fate processes. The findings highlight potential therapeutic targets for enhancing graft survival and function, emphasizing the importance of understanding the immunological aspects of transplant acceptance and longevity.

    Keywords: Type 1 diabetes (T1D), Islet Transplantation, Macrophages, Immune rejection, singlecell RNA sequencing (scRNA-seq), Syngeneic transplantation, Allogeneic transplantation, cytokine

    Received: 26 Mar 2024; Accepted: 02 Aug 2024.

    Copyright: © 2024 Mou, Lu, Wu and Pu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Zuhui Pu, Shenzhen Second People's Hospital, Shenzhen, Guangdong Province, China

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