Decidual IDO+ macrophage promotes the proliferation and restricts the apoptosis of trophoblasts

The metabolic characteristic of decidual immune cells and their unique properties in pregnancy loss*

“… 120 Similarly, IDO levels were lower in abortion cases than in normal early pregnancy 118,119,121 . Consistent with previous literatures, we found patients with URPL had a low level of IDO + dMφ and ovarian hormones, trophoblast and DSC, could upregulate IDO expression of dMφ 122 . Notably, IDO + dMφ displayed a M2 polarization bias that promoted trophoblast survival, facilitating the establishment and maintenance of normal pregnancy 122 .…”

“…118,119,121 Consistent with previous literatures, we found patients with URPL had a low level of IDO + dMφ and ovarian hormones, trophoblast and DSC, could upregulate IDO expression of dMφ. 122 Notably, IDO + dMφ displayed a M2 polarization bias that promoted trophoblast survival, facilitating the establishment and maintenance of normal pregnancy. 122 In cervical cancer cells, increased kynurenine induced the autophagy of cancer cells and promoted phagocytosis and activation of macrophage, thus inhibiting tumor growth.…”

“…122 Notably, IDO + dMφ displayed a M2 polarization bias that promoted trophoblast survival, facilitating the establishment and maintenance of normal pregnancy. 122 In cervical cancer cells, increased kynurenine induced the autophagy of cancer cells and promoted phagocytosis and activation of macrophage, thus inhibiting tumor growth. 123 However, the effect of kynurenine on macrophages at the maternal interface remains unclear.…”

The role of macrophages in reproductive-related diseases

“…Indoleamine 2, 3-dioxygenase (IDO), an intracellular cytoplasmic enzyme, transfers tryptophan (Trp) to N-formyl kynurenine [ 43 ]. IDO + dMφ is significantly lower in uRM patients than in normal control, and IDO + dMφ displayed M2 phenotype [ 44 ]. The expression of IDO was also reduced in the decidua of RM patients [ 45 ].…”

“…In a miscarriage mouse model, IDO supplementation reduced miscarriage rate by suppressing the inflammatory response [ 46 ]. Researchers have reported that IDO was a protective factor for early pregnancy, and that IDO and IDO + dMφ was reduced in uRM decidua [ 44 , 45 ], but researchers have also reported that IDO was elevated in uRM villi, and there is no significant difference in the expression of IDO in control decidua and in RM decidua [ 47 ]; thus, more studies are needed to prove the role of IDO in uRM. Cathepsin E is an intracellular aspartic protease belonging to the pepsin family [ 48 ].…”