Development and organization of omental milky spots.

The milky spots in omentum are atypical lymphoid tissues that play a pivotal role in regulating immune responses in the peritoneal cavity. The milky spots act as central hubs for collecting antigens and particles from the peritoneal cavity, regulating lymphocyte trafficking, promoting the differentiation and self-renewal of immune cells, and supporting the local germinal centre response. In addition, the milky spots exhibit unique developmental characteristics that combine the features of secondary and tertiary lymphoid tissues. These structures are innately programmed to form during foetal development; however, they can also be formed postnatally in response to peritoneal irritation such as inflammation, infection, obesity, or tumour metastasis. In this review, I discuss emerging perspectives on homeostatic development and organization of the milky spots.

Aberrant RNA sensing in regulatory T cells causes systemic autoimmunity.

Chronic and aberrant nucleic acid sensing causes type I IFN-driven autoimmune diseases, designated type I interferonopathies. We found a significant reduction of regulatory T cells (Tregs) in patients with type I interferonopathies caused by mutations in ADAR1 or IFIH1 (encoding MDA5). We analyzed the underlying mechanisms using murine models and found that Treg-specific deletion of Adar1 caused peripheral Treg loss and scurfy-like lethal autoimmune disorders. Similarly, knock-in mice with Treg-specific expression of an MDA5 gain-of-function mutant caused apoptosis of peripheral Tregs and severe autoimmunity. Moreover, the impact of ADAR1 deficiency on Tregs is multifaceted, involving both MDA5 and PKR sensing. Together, our results highlight the dysregulation of Treg homeostasis by intrinsic aberrant RNA sensing as a potential determinant for type I interferonopathies.