Enteric Glial Cells: A New Frontier in Neurogastroenterology and Clinical Target for Inflammatory Bowel Diseases

The word "glia" is derived from the Greek word "γλοια," glue of the enteric nervous system, and for many years, enteric glial cells (EGCs) were believed to provide mainly structural support. However, EGCs as astrocytes in the central nervous system may serve a much more vital and active role in the enteric nervous system, and in homeostatic regulation of gastrointestinal functions. The emphasis of this review will be on emerging concepts supported by basic, translational, and/or clinical studies, implicating EGCs in neuron-to-glial (neuroglial) communication, motility, interactions with other cells in the gut microenvironment, infection, and inflammatory bowel diseases. The concept of the "reactive glial phenotype" is explored as it relates to inflammatory bowel diseases, bacterial and viral infections, postoperative ileus, functional gastrointestinal disorders, and motility disorders. The main theme of this review is that EGCs are emerging as a new frontier in neurogastroenterology and a potential therapeutic target. New technological innovations in neuroimaging techniques are facilitating progress in the field, and an update is provided on exciting new translational studies. Gaps in our knowledge are discussed for further research. Restoring normal EGC function may prove to be an efficient strategy to dampen inflammation. Probiotics, palmitoylethanolamide (peroxisome proliferator-activated receptor-α), interleukin-1 antagonists (anakinra), and interventions acting on nitric oxide, receptor for advanced glycation end products, S100B, or purinergic signaling pathways are relevant clinical targets on EGCs with therapeutic potential.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially

Expression patterns of signaling lymphocytic activation molecule family members in peripheral blood mononuclear cell subsets in patients with systemic lupus erythematosus

Genome-wide linkage analysis studies (GWAS) studies in systemic lupus erythematosus (SLE) identified the 1q23 region on human chromosome 1, containing the Signaling Lymphocytic Activation Molecule Family (SLAMF) cluster of genes, as a lupus susceptibility locus. The SLAMF molecules (SLAMF1-7) are immunoregulatory receptors expressed predominantly on hematopoietic cells. Activation of cells of the adaptive immune system is aberrant in SLE and dysregulated expression of certain SLAMF molecules has been reported. We examined the expression of SLAMF1-7 on peripheral blood T cells, B cells, monocytes, and their respective differentiated subsets, in patients with SLE and healthy controls in a systematic manner. SLAMF1 levels were increased on both T cell and B cells and their differentiated subpopulations in patients with SLE. SLAMF2 was increased on SLE CD4+ and CD8+ T cells. The frequency of SLAMF4+ and SLAMF7+ central memory and effector memory CD8+ T cells was reduced in SLE patients. Naïve CD4+ and CD8+ SLE T cells showed a slight increase in SLAMF3 levels. No differences were seen in the expression of SLAMF5 and SLAMF6 among SLE patients and healthy controls. Overall, the expression of various SLAMF receptors is dysregulated in SLE and may contribute to the immunopathogenesis of the disease