Tolerance to non-inherited maternal antigen is sustained by LysM+ CD11c+ maternal microchimeric cells
Year: 2025
Type: article
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.
Source: Immunity
Authors: Yanyan Peng, Giang Pham, Jiahui Sun, Ujjwal Adhikari, Sudeep Kumar, Tzu-Yu Shao, Jeremy M. Kinder, Lucien H. Turner, Sing Sing Way
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $10,400
Funders: Howard Hughes Medical Institute, Burroughs Wellcome Fund, March of Dimes Foundation, National Institutes of Health, March of Dimes Prematurity Research Center Ohio Collaborative, National Heart, Lung, and Blood Institute, National Institute on Drug Abuse, National Institute of Allergy and Infectious Diseases
Awards: G1576472230, G1886068547, G2354209684, G3014393894, G4563812999, G4921210467, G6776325867, G7660896353, Immunological identity redefined by genetically foreign microchimeric cells, G8568292425, Vaccinology Training Program, Parity, paternity and pregnancy outcomes, Pregnancy induced deacetylation of sialylated glycoproteins, G970892991
OpenAlex ID: W4413911985