Microchimerism: The Hidden Cellular Dialogue Between Mother and Fetal That Shapes Lifelong Immunity.

Foetomaternal microchimerism establishes a lifelong reciprocal exchange of immune cells that shapes immunity in both mother and offspring. Foetal microchimeric cells (FMc) include CD34+ progenitors, CD8+ CTLs and Th2-polarized lymphocytes that integrate into maternal bone marrow, spleen and inflamed tissues, promoting peripheral tolerance via Treg (FOXP3+CD4+) expansion, CTLA-4 upregulation and IL-10/TGF-β secretion, while inhibiting CD8+ cytotoxicity through clonal deletion and CXCR3 downregulation. Conversely, maternal microchimerism (MMc) transfers memory T cells, CD34+ HSCs and innate effectors (macrophages, NK cells) to the foetal thymus and lymphoid tissues, driving NIMA-specific Treg differentiation via CNS1-dependent Foxp3 induction and PD-L1+ DC suppression of Th1/Th17 responses. HLA class II incompatibility, complement (C3/C5a) and CCL2/CCR2 signalling coordinate this cellular crosstalk. Clinically, FMc enhances maternal tissue repair and cancer surveillance but increases autoimmune risk in scleroderma and PBC; MMc boosts newborn pathogen resistance and reduces GVHD in NIMA-matched HSCT. This review establishes microchimerism as a crucial regulator of intergenerational immunological homeostasis.