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Rat Enteric Glial Cells Express Novel Isoforms of Interleukine-7 Regulated During Inflammation

Laetitia Kermarrec, Tony Durand, Jacques Gonzales, Julie Pabois, Philippe Hulin, Michel Neunlist, Isabelle Neveu, Philippe Naveilhan

Neurogastroenterol Motil. 2019 Jan;31(1):e13467.

PMID: 30240048

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
IAR42413274 IL-7 from rat IL-7 from rat Price
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