Rat enteric glial cells express novel isoforms of Interleukine‐7 regulated during inflammation

• Published in: Neurogastroenterology and motility Vol. 31; no. 1; pp. e13467 - n/a
• Main Authors: Kermarrec, Laetitia, Durand, Tony, Gonzales, Jacques, Pabois, Julie, Hulin, Philippe, Neunlist, Michel, Neveu, Isabelle, Naveilhan, Philippe
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2019; Wiley
• Subjects: Animals; Cell death; Cell survival; cytokine; Cytokines; Digestive system; Enteric nervous system; Female; Gastrointestinal tract; Glial cells; Homeostasis; IL‐1; Immunology; Inflammation; Inflammation - immunology; Inflammatory diseases; Interleukin-7; Interleukin-7 - biosynthesis; Interleukin-7 - immunology; Intestine; Intestine, Small; Intestine, Small - immunology; Intestine, Small - innervation; Isoforms; Life Sciences; Lymphocytes T; mRNA; Nervous system; Neuroglia; Neuroglia - immunology; Neuroimmunomodulation; Neuroimmunomodulation - immunology; neuron; Neuronal-glial interactions; Neurons; Neurons - immunology; Neurons and Cognition; Protein Isoforms; Rats; Rats, Sprague-Dawley; Rodents; splice variant; Submucosal plexus; Submucous Plexus; Submucous Plexus - immunology; T cell; T-Lymphocytes; T-Lymphocytes - immunology; TNF; Tumor necrosis factor-α; cytokine; IL-1; T cell; neuron; enteric nervous system; TNF; splice variant
• ISSN: 1350-1925; 1365-2982; 1365-2982
• DOI: 10.1111/nmo.13467

Background Neuroimmune interactions are essential to maintain gut homeostasis and prevent intestinal disorders but so far, the impact of enteric glial cells (EGC) on immune cells remains a relatively unexplored area of research. As a dysregulation of critical cytokines such as interleukine‐7 (IL‐7) was suggested to exacerbate gut chronic inflammation, we investigated whether EGC could be a source of IL‐7 in the gastrointestinal tract. Methods Expression of IL‐7 in the rat enteric nervous system was analyzed by immunochemistry and Q‐PCR. IL‐7 variants were cloned and specific antibodies against rat IL‐7 isoforms were raised to characterize their expression in the submucosal plexus. IL‐7 isoforms were produced in vitro to analyze their impact on T‐cell survival. Key Results Neurons and glial cells of the rat enteric nervous system expressed IL‐7 at both mRNA and protein levels. Novel rat IL‐7 isoforms with distinct C‐terminal parts were detected. Three of these isoforms were found in EGC or in both enteric neurons and EGC. Exposure of EGC to pro‐inflammatory cytokines (IL‐1β and/or TNFα) induced an upregulation of all IL‐7 isoforms. Interestingly, time‐course and intensity of the upregulation varied according to the presence or absence of exon 5a in IL‐7 variants. Functional analysis on T lymphocytes revealed that only canonical IL‐7 protects T cells from cell death. Conclusions and Inferences IL‐7 and its variants are expressed by neurons and glial cells in the enteric nervous system. Their distinct expression and upregulation in inflammatory conditions suggest a role in gut homeostasis which could be critical in case of chronic inflammatory diseases. We found new isoforms of interleukin‐7 which are expressed by neurons but also glial cells in the rat enteric nervous system. Interestingly, pro‐inflammatory cytokines upregulate IL‐7 isoforms in glial cells with distinct time‐course and intensity.