Contactin-1 Is Required for Peripheral Innervation and Immune Homeostasis Within the Intestinal Mucosa.

Frontiers in Immunology
Marisol VenyJohn R Šedý

Abstract

Neuronal regulation of diverse physiological functions requires complex molecular interactions in innervated tissues to maintain proper organ function. Here we show that loss of the neuronal cell surface adhesion/recognition molecule Contactin-1 (Cntn1) directly impairs intestinal function causing wasting that subsequently results in global immune defects. Loss of Cntn1 results in hematologic alterations and changes in blood metabolites associated with malnourishment. We found thymus and spleen of Cntn1-deficient animals atrophied with severe reductions in lymphocyte populations. Elevated thymic Gilz expression indicated ongoing glucocorticoid signaling in Cntn1-deficient animals, consistent with the malnourishment phenotype. Intestinal Contactin-1 was localized to neurons in the villi and the submucosal/myenteric plexus that innervates smooth muscle. Loss of Cntn1 was associated with reduced intestinal Bdnf and Adrb2, indicating reduced neuromuscular crosstalk. Additionally, loss of Cntn1 resulted in reduced recruitment of CD3+ T cells to villi within the small intestine. Together, these data illustrate the critical role of Contactin-1 function within the gut, and how this is required for normal systemic immune functions.

References

Jun 1, 1991·The American Journal of Physiology·L CoderreJ L Chiasson
Jan 1, 1986·Current Topics in Pathology. Ergebnisse Der Pathologie·N Dourov
Oct 19, 1999·The Journal of Clinical Investigation·J K HowardS R Bloom
Jul 29, 2000·Methods in Enzymology·I RooneyC F Ware
Aug 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Judson A BrewerLouis J Muglia
Dec 20, 2003·Nature Reviews. Neuroscience·Sebastian Poliak, Elior Peles
May 23, 2008·Journal of Leukocyte Biology·Amanda L Gruver, Gregory D Sempowski
Jul 7, 2009·Annual Review of Psychology·Florian Holsboer, Marcus Ising
Jun 18, 2011·Nature Reviews. Immunology·Hilde CheroutreDaniel Mucida
Feb 9, 2012·The Journal of Biological Chemistry·Ji-Yeun HurLars O Tjernberg
May 15, 2013·Nature Reviews. Immunology·Freddy RadtkeFabienne Tacchini-Cottier
Jan 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Gülsen ÇolakoğluBarbara Ranscht
Jan 16, 2014·Mucosal Immunology·D R MathernS Dahan
May 21, 2014·Human Molecular Genetics·Vladimir VacicAvi Orr-Urtreger
Sep 12, 2015·World Journal of Gastroenterology : WJG·De-Hu ChenBo-Jian Jiang
Dec 1, 2015·Frontiers in Endocrinology·Simona RonchettiCarlo Riccardi
May 8, 2016·Cell·Henrique Veiga-Fernandes, Daniel Mucida
Jul 8, 2016·Nature·Kenya Honda, Dan R Littman
Jul 21, 2016·Nature Reviews. Gastroenterology & Hepatology·Meenakshi Rao, Michael D Gershon
Nov 23, 2016·Molecular and Cellular Neurosciences·Gianfranco GennariniAndrew J W Furley
Feb 23, 2017·Annual Review of Immunology·Jakub Abramson, Graham Anderson
Dec 12, 2018·Neural Regeneration Research·Madhurima ChatterjeeCharlotte E Teunissen
Jul 20, 2019·Parkinson's Disease·Bodil Ohlsson, Elisabet Englund
Dec 19, 2019·Nature Reviews. Immunology·Jun R Huh, Henrique Veiga-Fernandes

❮ Previous
Next ❯

Citations

Feb 25, 2021·Neurogastroenterology and Motility : the Official Journal of the European Gastrointestinal Motility Society·Arjun SinghSatish Rattan
Aug 25, 2021·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Chase KingsburyCesario V Borlongan

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
confocal microscopy

Software Mentioned

VetScan

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.