Kato M, Negishi Y, Shima Y, et al. - A primary cause of preterm birth (PB) is acute chorioamnionitis (aCAM) associated with microbial infection. Recent studies reporting the causative role of innate immunity and sterile inflammation for PB in the absence of aCAM led researchers to analyze immune cells in the decidua of early to moderate PB without aCAM. Patients with PB at a gestational age of 24⁺⁰ to 33⁺⁶ weeks without aCAM in pathological diagnosis were divided into two groups: Patients with labor and/or rupture of membrane (ROM) (no aCAM with labor and/or ROM: nCAM‐w‐LR), and patients without labor and/or ROM (no aCAM without labor and/or ROM: nCAM‐w/o‐LR). Deciduas obtained from patients in the nCAM‐w‐LR group showed an accumulation of iNKT cells, and raised expression of HMGB1, TLR4, receptors for advanced glycation end‐products, and CD1d on DCs and macrophages. HMGB1 promoted the proliferation of iNKT cells co‐cultured with DCs and macrophages, which was identified to be inhibited by heparin. Findings suggest that in human pregnancy, inappropriate activation of innate immune cells and increased HMGB1 expression may represent parturition signs. Hence, indicating the possible utility of controlling these cells and HMGB1 antigenicity as a potential therapeutic target for the prevention of PB.