Fig. 8: Schematic diagram of functional regulation of Tim-3+Mφs on maternal-fetal tolerance. | Cell Death & Disease

Fig. 8: Schematic diagram of functional regulation of Tim-3+Mφs on maternal-fetal tolerance.

From: Tim-3+ decidual Mφs induced Th2 and Treg bias in decidual CD4+T cells and promoted pregnancy maintenance via CD132

Fig. 8

Previously we reported that Tros directly contributed to the Tim-3, PD-1 and CTLA-4 expression on dCD4+T cells. These checkpoint pathways, in turn, may operate within the functional immune-modulatory network not only to promote maternal-fetal tolerance but also improved Tros function. The current study demonstrated that Tros also induced the higher Tim-3 expression on dMφs during normal pregnancy in HLA-C dependent manner. Neither Tim-3+ nor Tim-3−dMφs population can be categorized as strictly M1 or M2. With higher CD132 expression, Tim-3+dMφs induced Th2 and Treg bias in dCD4+T cells and promoted pregnancy maintenance. The reduced abundance of Tim-3 on Mφs was accompanied by disordered anti- and pro-inflammatory cytokine profiles in miscarriage. Blockade of Tim-3 or CD132 pathways leaded to the dysfunction of maternal-fetal tolerance and increased fetal loss. While IL-4 treated Tim-3−Mφs, via unknown receptor, could rescue the fetal resorption induced by Mφ depletion.

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