Neural regulation of inflammation and metabolism

Overactive inflammation causes increased morbidity and mortality, not least in cardiovascular disease, the most common cause of death in the world. A better understanding of the molecular and cellular mechanisms that drive disease development promises better opportunities for treatment and prevention.

Team Olofsson is one of the teams within the research group Pathophysiological mechanisms of cardiovascular and inflammatory diseases

Our research

In the video above, Peder Olofsson and Henrik Hult (KTH) present how they research bioelectronic medicine within the interdisciplinary center MedTechLabs. The film is produced by MikeyKay Films.

Understanding the pathophysiology of cardiovascular disease and overactive inflammation requires neuroscience because nerve signals regulate inflammation and metabolism. We have uncovered cellular and molecular mechanisms for neural regulation of inflammation and recently showed that activation of specific peripheral nerves controls the active healing of inflammation (Caravaca et al., PNAS 2022) and work in one of the European consortia we participate in found that specific nerve signals affect the development of atherosclerosis (Mohanta et al., Nature 2022) (Fig. 1).

In the long term, we aim to create both an atlas and a dictionary of how neural reflexes regulate inflammation and metabolism, i.e. the 1) peripheral neuroanatomy and neurophysiology, and 2) cellular and molecular mechanisms of excessive inflammation (Fig. 2). We work toward this goal together with engineers at KTH and Linköping University within the Stockholm Center for Bioelectronic Medicine at MedTechLabs.

The figure illustrates what is written in the caption text.
Figure 1. Understanding cardiovascular inflammation requires neuroscience. Discoveries over recent decades showed that 1) atherosclerosis is an inflammatory disease and 2) neural reflexes regulate inflammation. Recent discoveries show that neural regulation plays a role in the pathogenesis of cardiovascular disease. Very little is known about these mechanisms, and this is a focus area in the group.
The figure illustrates what is written in the caption text.
Figure 2. Neural signals regulate inflammation and metabolism. (a) The brain coordinates organ function using peripheral nerves that reach virtually every tissue and cell. (b, c) Signals are propagated using electrical impulses and chemicals, i.e. neurotransmitters such as norepinephrine and acetylcholine. (d) Nerves have receptors that respond to mediators of inflammation, infection, and tissue damage.

Cooperation

  • Henrik Hult, KTH, Stockholm: Mapping neural signals that regulate of inflammation.
  • Magnus Berggren, LiU, Linköping: Improving machine-perihperal nerve interfaces.
  • Molly Stevens, Imperial College, London: Neural regulation of the foreign body response.
  • Andreas Habenicht and Saroj Mohanta, LMU, Munich: Neural regulation of atherosclerosis.
  • Kevin J Tracey, The Feinstein Institute, New York: Neural regulation of inflammation.

Research support

  • The Swedish Research Council
  • Heart-Lung Foundation
  • SSF
  • MedTechLabs
  • ALF
  • NovoNordisk
  • Karolinska Institutet

Contact

Peder Olofsson

Principal researcher

 

Selected publications

Vagus nerve stimulation promotes resolution of inflammation by a mechanism that involves Alox15 and requires the α7nAChR subunit.
Caravaca AS, Gallina AL, Tarnawski L, Shavva VS, Colas RA, Dalli J, Malin SG, Hult H, Arnardottir H, Olofsson PS
Proc Natl Acad Sci U S A 2022 05;119(22):e2023285119.

Adenylyl Cyclase 6 Mediates Inhibition of TNF in the Inflammatory Reflex.
Tarnawski L, Reardon C, Caravaca AS, Rosas-Ballina M, Tusche MW, Drake AR, Hudson LK, Hanes WM, Li JH, Parrish WR, Ojamaa K, Al-Abed Y, Faltys M, Pavlov VA, Andersson U, Chavan SS, Levine YA, Mak TW, Tracey KJ, Olofsson PS
Front Immunol 2018 ;9():2648.

Choline acetyltransferase-expressing T cells are required to control chronic viral infection.
Cox MA, Duncan GS, Lin GHY, Steinberg BE, Yu LX, Brenner D, Buckler LN, Elia AJ, Wakeham AC, Nieman B, Dominguez-Brauer C, Elford AR, Gill KT, Kubli SP, Haight J, Berger T, Ohashi PS, Tracey KJ, Olofsson PS, Mak TW
Science 2019 02;363(6427):639-644.

Blood pressure regulation by CD4+ lymphocytes expressing choline acetyltransferase.
Olofsson PS, Steinberg BE, Sobbi R, Cox MA, Ahmed MN, Oswald M, Szekeres F, Hanes WM, Introini A, Liu SF, Holodick NE, Rothstein TL, Lövdahl C, Chavan SS, Yang H, Pavlov VA, Broliden K, Andersson U, Diamond B, Miller EJ, Arner A, Gregersen PK, Backx PH, Mak TW, Tracey KJ
Nat Biotechnol 2016 Oct;34(10):1066-1071.

Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit.
Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ
Science 2011 Oct;334(6052):98-101.

A novel flexible cuff-like microelectrode for dual purpose, acute and chronic electrical interfacing with the mouse cervical vagus nerve.
Caravaca AS, Tsaava T, Goldman L, Silverman H, Riggott G, Chavan SS, Bouton C, Tracey KJ, Desimone R, Boyden ES, Sohal HS, Olofsson PS
J Neural Eng 2017 12;14(6):066005.

Prevention of radiotherapy-induced arterial inflammation by interleukin-1 blockade.
Christersdottir T, Pirault J, Gisterå A, Bergman O, Gallina AL, Baumgartner R, Lundberg AM, Eriksson P, Yan ZQ, Paulsson-Berne G, Hansson GK, Olofsson PS, Halle M
Eur Heart J 2019 08;40(30):2495-2503.

Prolonged elevation of plasma HMGB1 is associated with cognitive impairment in intensive care unit survivors.
Brück E, Lasselin J, , Andersson U, Sackey PV, Olofsson PS
Intensive Care Med 2020 04;46(4):811-812.

Neuroimmune cardiovascular interfaces control atherosclerosis.
Mohanta SK, Peng L, Li Y, Lu S, Sun T, Carnevale L, Perrotta M, Ma Z, Förstera B, Stanic K, Zhang C, Zhang X, Szczepaniak P, Bianchini M, Saeed BR, Carnevale R, Hu D, Nosalski R, Pallante F, Beer M, Santovito D, Ertürk A, Mettenleiter TC, Klupp BG, Megens RTA, Steffens S, Pelisek J, Eckstein HH, Kleemann R, Habenicht L, Mallat Z, Michel JB, Bernhagen J, Dichgans M, D'Agostino G, Guzik TJ, Olofsson PS, Yin C, Weber C, Lembo G, Carnevale D, Habenicht AJR
Nature 2022 05;605(7908):152-159.

Targeting T cell costimulation to prevent atherothrombosis.
Olofsson PS
Circ Res 2012 Mar;110(6):800-1.