Advances in immune checkpoint-based immunotherapies for multiple sclerosis: rationale and practice.

Beyond the encouraging results and broad clinical applicability of immune checkpoint (ICP) inhibitors in cancer therapy, ICP-based immunotherapies in the context of autoimmune disease, particularly multiple sclerosis (MS), have garnered considerable attention and hold great potential for developing effective therapeutic strategies. Given the well-established immunoregulatory role of ICPs in maintaining a balance between stimulatory and inhibitory signaling pathways to promote immune tolerance to self-antigens, a dysregulated expression pattern of ICPs has been observed in a significant proportion of patients with MS and its animal model called experimental autoimmune encephalomyelitis (EAE), which is associated with autoreactivity towards myelin and neurodegeneration. Consequently, there is a rationale for developing immunotherapeutic strategies to induce inhibitory ICPs while suppressing stimulatory ICPs, including engineering immune cells to overexpress ligands for inhibitory ICP receptors, such as program death-1 (PD-1), or designing fusion proteins, namely abatacept, to bind and inhibit the co-stimulatory pathways involved in overactivated T-cell mediated autoimmunity, and other strategies that will be discussed in-depth in the current review. Video Abstract.

Autophagy-mediated immune system regulation in reproductive system and pregnancy-associated complications.

Autophagy lysosomal degradation is the main cell mechanism in cellular, tissue and organismal homeostasis and is controlled by autophagy-related genes (ATG). Autophagy has important effects in cellular physiology, including adaptation to metabolic stress, removal of dangerous cargo (such as protein aggregates, damaged organelles, and intracellular pathogens), regeneration during differentiation and development, and prevention of genomic damage in general. Also, it has been found that autophagy is essential for pre-implantation, development, and maintaining embryo survival in mammals. Under certain conditions, autophagy may be detrimental through pro-survival effects such as cancer progression or through possible cell death-promoting effects. Hormonal changes and environmental stress can initiate autophagy in reproductive physiology. The activity of autophagy can be upregulated under conditions like a lack of nutrients, inflammation, hypoxia, and infections. In this regard the dysregulation of autophagy involved in some pregnancy complications such as preeclampsia (PE) and pregnancy loss, and has a major impact on reproductive outcomes. Therefore, we aimed to discuss the relationship between autophagy and the female reproductive system, with a special focus on the immune system, and its role in fetal and maternal health.