The Axonal Guidance Receptor Neogenin Promotes Acute Inflammation

Klemens König,Valbona Mirakaj,Dimitra Gatidou,Peter Rosenberger,Jens Meier,Tiago Granja,Holger K Eltzschig

doi:10.1371/journal.pone.0032145

Klemens König, Valbona Mirakaj + Show 5 more

Open Access

https://doi.org/10.1371/journal.pone.0032145

Copy DOI

Abstract

Neuronal guidance proteins (NGP) were originally described in the context of axonal growth and migration. Yet recent work has demonstrated that NGPs also serve as guidance cues for immune competent cells. A crucial target receptor for NGPs during embryonic development is the neogenin receptor, however its role during acute inflammation is unknown. We report here that neogenin is abundantly expressed outside the nervous system and that animals with endogenous repression of neogenin (Neo1−/−) demonstrate attenuated changes of acute inflammation. Studies using functional inhibition of neogenin resulted in a significant attenuation of inflammatory peritonitis. In studies employing bone marrow chimeric animals we found the hematopoietic presence of Neo1−/− to be responsible for the attenuated inflammatory response. Taken together our studies suggest that the guidance receptor neogenin holds crucial importance for the propagation of an acute inflammatory response and further define mechanisms shared between the nervous and the immune system.

Highlights

Inflammatory conditions such as sepsis are marked by acute inflammatory changes within the affected tissue sites
Several families of these neuronal guidance proteins (NGP)s were described outside the central nervous system (CNS), amongst these are the slits, semaphorins, netrins and the repulsive guidance protein family, where they act as guidance cues for the migration of granulocytes, lymphocytes, monocytes and dendritic cells [5,6,7,8,9,10,11]
Neogenin is expressed in murine tissues ouside the CNS We initially addressed the question whether Neo1 is expressed in murine organs outside the central nervous system to validate our model subsequently used

Summary

Introduction

Inflammatory conditions such as sepsis are marked by acute inflammatory changes within the affected tissue sites. A role for RGM-A was described during multiple sclerosis by Muramatsu et al In this study the authors demonstrated that exposure of RGMA to CD4(+) T cells led to activation of the small GTPase Rap and increased adhesion of T cells to intracellular adhesion molecule-1 [5]. This implies that neogenin holds an intrinsic role during inflammatory events that is not known to date

Objectives

Methods

Results

Conclusion