美国辛辛那提大学Sing Sing Way研究组发现，对非遗传性母源抗原的耐受性由LysM⁺ CD11c⁺母源微嵌合细胞维持。2025年9月2日，国际知名学术期刊《免疫学》发表了这一成果。

研究了具有非遗传性母源抗原（NIMA）耐受性的母源微嵌合细胞（MMc）。完全的MMc缺失推翻了NIMA特异性耐受的标志性特征，包括FOXP3⁺调节性T细胞扩增和跨代抗胎儿流失的弹性。逐步减少单个MMc亚群表明，母细胞LysM⁺ CD11c⁺ Vav1⁺白细胞的微嵌合完全维持了NIMA特异性耐受性。有趣的是，这些耐受性细胞的条件耗竭并不会降低整体MMc水平，从而将NIMA特异性耐受性与MMc持久性分离开来。它们对母体异体抗原的耐受性仅由一小部分由LysM和CD11c共表达鉴定的MMc维持，其余MMc的持久性突出了在早期发育背景下获得的对异体母体细胞的显著适应性。

据介绍，母胎微嵌合越来越多地与炎症疾病和免疫耐受表型相关。然而，在靶组织中发现微嵌合细胞并不能建立诱导性，这需要操纵这些罕见的异质细胞的平台。

附：英文原文

Title: Tolerance to non-inherited maternal antigen is sustained by LysM+ CD11c+ maternal microchimeric cells

Author: Yanyan Peng, Giang Pham, Jiahui Sun, Ujjwal Adhikari, Sudeep Kumar, Tzu-Yu Shao, Jeremy M. Kinder, Lucien H. Turner, Sing Sing Way

Issue&Volume: 2025-09-02

Abstract: Maternal-fetal microchimerism is increasingly linked with both inflammatory disorders and immune tolerance phenotypes. However, finding microchimeric cells in target tissues does not establish causality, which require platforms for manipulating these rare and heterogeneous cells. Here, we studied maternal microchimeric cells (MMc) that sustain non-inherited maternal antigen (NIMA) tolerance. Complete MMc depletion overturned hallmark features of NIMA-specific tolerance including FOXP3+ regulatory T cell expansion and cross-generational resiliency against fetal wastage. Stepwise depletion of individual MMc subsets showed that NIMA-specific tolerance is sustained exclusively by microchimerism in maternal LysM+ CD11c+ Vav1+ leukocyte cells. Interestingly, conditional depletion of these tolerogenic cells does not diminish overall MMc levels, dissociating NIMA-specific tolerance from MMc persistence. Thus, tolerance to maternal alloantigens is maintained by only a small fraction of MMc identified by LysM and CD11c co-expression, with persistence of remaining MMc highlighting remarkable adaptation to allogeneic maternal cells acquired in this early-life developmental context.

DOI: 10.1016/j.immuni.2025.08.005

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00368-1