In this Research Topic of Frontiers in Immunology focused on the steroids and secosteroids in the modulation of inflammation and immunity 11 articles by experts in corresponding fields have been published (Bier et al.; Bruscoli et al.; He et al.; König et al.; Lucafò et al.; Merk et al.; Postlethwaite et al.; Quatrini et al.; Shimba et al.; Vanderhaeghen et al.; Xie et al.). These included research articles, reviews and mini-reviews papers on important aspects of steroid-and secosteroidogenesis and the role of the final or intermediate products of these pathways in regulation of inflammatory and immune activities. Mechanisms of action and of broad homeostatic activities in humans and experimental animal models have also been discussed in these expert written papers. Different aspects of biochemistry, molecular biology, cell biology, and the systems-level role of (seco) steroidogenesis in regulating physiology and pathology have been discussed.

The key role in steroidogenesis is played by an enzyme CYP11A1, a member of the cytochrome P450 family, which catalyzes the first and rate-limiting step in steroidogenesis, converting cholesterol to pregnenolone through sequential its hydroxylation at C22 and C20, with a final cleavage of the side chain (1–4). In addition to the adrenals, gonads and placenta (classical steroidogenic tissues), CYP11A1 is also expressed in the brain (6), gastrointestinal tract, immune systems (7–9), the skin (5) and other peripheral organs/tissues (10) including malignant tumors (9, 11). The roles of local steroidogenesis (ie, extra-glandular steroidogenesis, including immune cell mediated steroidogenesis) are emerging and warrant a revisit to this important biosynthetic pathway and its functional involvement in tissue homeostasis (including immune homeostasis) and disease (7, 12, 13). Recent discoveries pointed out an important, and unexpected role for CYP11A1 in metabolism of 7-dehydrocholestrol (14), vitamin D3 (15), D2 (16), lumisterol (17, 18) and ergosterol (11) to several biologically active metabolites. Thus, CYP11A1 activity is opening several novel pathways generating∆ 7 steroids, full chain and short chain lumisterol derivatives, and secosteroids (vitamin D hydroxyderivatives)(5, 19). While the biological significance of these pathways is currently being evaluated, it must be noted that CYP11A1-derived hydroxyderivatives of vitamin D (20, 21) and of lumisterol (18) are circulating in human serum and are detectable in the epidermis. Furthermore, recent data showing that 7-Dehydrocholesterol reductase (DHCR7, which catalyzes the reduction of the C7-C8 double bond of its B-ring that is necessary for the final formation of cholesterol) did not act on 7-dehydropregnenolone and lumisterol compounds (22), enhances the importance of pathways generating∆ 7 steroids and lumisterol derivatives (20, 23, 24).