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Necrotizing enterocolitis (NEC) is a devastating neonatal gastrointestinal emergency. Fucosylated glycans on intestinal epithelial cells (IECs) play a central role in the maintenance of intestinal homeostasis. Nevertheless, its association with necrotizing enterocolitis is not clear. We examined paraffin-embedded intestinal specimens from participants and found that the NEC patients showed lower intestinal epithelial fucosylation levels than the control patients. In the mouse model of NEC, the percentage of fucosylated epithelial cells (F-ECs) and ILC3s was decreased. Also, the expression levels of IL-22 and Fut2 were reduced. Moreover, the critical role of epithelial fucosylation in NEC was further confirmed by administering the anti-IL-22 antibody, which caused an increase in histological damage, body weight loss, intestinal permeability and proinflammatory cytokine release correlated with a reduction of F-ECs. Overall, intestinal fucosylation deficiency led to increased susceptibility and severity of NEC. Further studies are needed to determine whether modification of intestinal fucosylation affects the development of NEC.

Hematopoietic development occurs in the bone marrow, and this process begins with hematopoietic stem cells (HSCs). Ubc9 is a unique E2-conjugating enzyme required for SUMOylation, an evolutionarily conserved post-translational modification system. We herein show that a conditional Ubc9 deletion in the hematopoietic system caused decreased thymus weight and reduced lymphocyte to myeloid cell ratio. Importantly, Ubc9 deletion in the hematopoietic system only selectively impaired the development of common lymphoid progenitors (CLPs) in the bone marrow and perturbed their potential to differentiate into lymphocytes, thereby decreasing the number of T/B cells in the periphery. Ubc9 was found to be required for CLP viability, and therefore, Ubc9 deficiency rendered CLPs to undergo apoptosis and attenuated their proliferation. Thus, Ubc9 plays a critical role in the regulation of CLP function during hematopoietic development in the bone marrow.

Autophagy is an evolutionarily conserved catabolic process that directs cytoplasmic proteins, organelles and microbes to lysosomes for degradation. It not only represents an essential cell-intrinsic mechanism to protect against internal and external stresses but also shapes both innate and adaptive immunity. Regulatory T cells (Tregs) are a developmentally and functionally distinct T cell subpopulation engaged in sustaining immunological self-tolerance and homeostasis. There is compelling evidence that autophagy is actively regulated in Tregs and serves as a central signal-dependent controller for Tregs by restraining excessive apoptotic and metabolic activities. In this review, we discuss how autophagy modulates the stability and functionality of Tregs in different disease settings, and provide a perspective on how manipulation of autophagy enables better control of immune response by targeting the generation of Tregs and the maintenance of their stability.