Multiple sclerosis (MS) is an inflammatory degenerative disease of the central nervous system (CNS) (Dolati et al., 2017; Gharibi et al., 2015). Although the etiology of MS is unknown, it is clear that autoreactive T cells drive immune-mediated damage to the myelin sheath around nerve axons, causing neurological loss over time (Jadidi-Niaragh and Mirshafiey, 2011). Recently, the role of a newly isolated immunity cells population, innate lymphoid cells (ILC) in the pathogenesis of MS, has been discussed in numerous studies (Spits et al., 2013; Elemam et al., 2017; Ebbo et al., 2017).

ILCs are a group of immune cells that provide the first line of defense against various pathogens and are involved in tissue repair and inflammation. These cells are characterized by several features, including the absence of antigen receptors dependent on RAG recombinase, lymphoid morphology, and the absence of myeloid phenotypic markers, therefore they are called cells that are negative for the cell lineage markers (CD3−/CD19−) (Neill et al., 2010). ILC classification is based on transcription factors, surface molecules, and the profile of produced cytokines. At the same time, 3 groups are mainly distinguished: ILC1, ILC2, and ILC3 (Spits et al., 2013). ILC1s are composed of NK cells as well as non-cytotoxic ILC1s that secrete IFN-γ and express T-bet. ILC2s are determined by GATA3 and CRTH2 expression and have the ability to produce Th2-type cytokines. ILC3 express RORγt and c-kit, include ILC3 and lymphoid tissue inducers (LTi) that secrete IL-17 and/or IL-22 (Ebbo et al., 2017). These cells are capable of interacting with both commensal and pathogenic flora (Satoh-Takayama et al., 2008; Hepworth et al., 2015).

It is known that the frequency of MS in women is much higher than in men (Harbo et al., 2013). At the same time, it was found that during pregnancy there is a weakening of the manifestations of Th1-mediated autoimmune pathologies, including MS (Pelfrey et al., 2005; Neuteboom et al., 2012). Given that the gestational process is accompanied by significant hormonal changes, it can be assumed that placental hormones are the factors that weaken the course of MS. Estriol (E3) is one of possible candidates for the regulation of immune cell functions in MS (Sicotte et al., 2002; Voskuhl et al., 2016). Its level increases from the 7th week of pregnancy until childbirth by almost 10 times, while in non-pregnant women E3 is produced in very small quantities and is practically not detected. It has been shown that this hormone is able to effectively regulate leukocytes functions in both healthy donors and MS patients (Nekrasova and Shirshev, 2013, 2020; Shirshev et al., 2017, 2018; Soldan et al., 2003; Papenfuss et al., 2011).

The purpose of this work was to investigate the phenotypic characteristics of ILC from MS patients in comparison with healthy donors ex vivo and after 48 h incubation with E3 and commensal microflora cells.