Intestinal brush border formation requires a TMIGD1-based intermicrovillar adhesion complex.

Intestinal epithelial cells absorb nutrients through the brush border, composed of dense arrays of highly ordered microvilli at their apical membranes. A protocadherin-based intermicrovillar adhesion complex localized at microvilli tips mediates microvilli packing and organization. Here, we identified a second adhesion complex localized at the proximal base region of microvilli. This complex contained the immunoglobulin superfamily member TMIGD1, which directly interacted with the microvillar scaffolding proteins EBP50 and E3KARP. Complex formation with EBP50 required the activation of EBP50 by the actin-binding protein ezrin and was enhanced by the dephosphorylation of Ser162 in the PDZ2 domain of EBP50 by the phosphatase PP1α. Binding of the EBP50-ezrin complex to TMIGD1 enhanced the dynamic turnover of EBP50 at microvilli. Enterocyte-specific inactivation of Tmigd1 in mice resulted in microvillar blebbing, loss of intermicrovillar adhesion, and perturbed brush border formation. Thus, we identified a second adhesion complex in microvilli and propose a mechanism that promotes microvillar formation and dynamics.

Lipid metabolism as a mechanism of immunomodulation in macrophages: the role of liver X receptors.

Macrophages are immune myeloid cells with an extreme ability to modulate their phenotype in response to insults and/or pathogens. The immunomodulatory capacity of macrophages is also patent during development as they adapt their phenotype to the host tissue environment establishing the heterogeneous populations of tissue-resident macrophages. An important mechanism of immunomodulation in macrophages occurs through the regulation of transcriptional activity. Numerous transcription factors are associated with macrophage plasticity, among them, several nuclear receptors. The nuclear receptors Liver X Receptors (LXRα and LXRß) have also revealed as active players during macrophage adaptations in diverse scenarios. This review will address the different mechanisms by which LXRs contribute to immunomodulation in macrophages by connecting lipid metabolism and immunity through transcriptional regulation.