Download Fa y Acids In Mul ple Sclerosis: Length Ma ers For

FaLyAcidsInMulEpleSclerosis:
LengthMaLersForAutoimmunityOrTherapeuEcPotenEal
1,StefanieJörg2,JohannesBerg1,
AidenHaghikia1,AlexanderDuscha
RalfA.Linker2*,RalfGold1*
1Department
of Neurology, Ruhr-University Bochum, Germany
2Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, Germany
ObjecEve:Toinves)gatetheimpactoforalpropionate(PA)–ashortchainfa9yacid(SCFA)-onregulatoryTcells(Treg)invivoinhealthy
volunteersandMSpa)ents.
Background:Wehaverecentlyshownthatdependingontheirchainlengthfa9yacids(FA)eitherincreaseTh17differen)a)on(longchainFA,
LCFA)orTreg(SCFA)intheinthesmallintes)ne.Furthermore,wecouldshowthatwhilelongchainFAhaveadetrimentaleffectonthecourse
oftheMOGinducedexperimentalmodelofmul)plesclerosis,theexperimentalautoimmuneencephalomyeli)s(EAE),SCFAameliorateEAE
mainlybypromo)ngthedifferen)a)onofTreg.
Design/Methods:Inaproofofconceptstudywetransferredourobserva)onsonPAtohealthyindividualsandMSpa)entsbyorally
administra)ngPA(1gdaily)–anapprovedfoodaddi)vewithnosafetyconcerns-incapsulesfor14-60days.Thestudyincludedwashout
intervalsaSer14-60days.AdetailedimmunophenotypicassessmentofTcellsubsetsbeforeandatseveral)mepointsaSerPAintakewas
performed,aswellasaddi)onalfunc)onalcorrelates,suchasinvitrosuppressionassays.
A
A)Inarecentstudy,weshoweddiet-inducedchanges
inthegutalterthefateandcomposi)onofThelper
cell-popula)onsinsidethesmallintes)ne.WhileLCFA
support the differen)a)on of naive T cells to
proinflammatory Th17 cells in vitro, SCFA,
predominantlyPA(C3),enhancethedifferen)a)onto
Treg. Consistent with this findings, LCFA-based diet
severedthediseasecourseinMOG-immunizedEAE.
ViceversaoralgavageofPAonadailybasisleadsto
significantameliora)onofEAEcourse(Haghikiaetal.
2015).
B/C) In a first proof of concept
study we assessed different T cell
subsets (Th1; Th17; Treg) of
healthy individuals before and
aSer 14 days of PA intake (Fig. B
shows the study design). PA was
given twice a day on (2x 500 mg).
We observed a highly significant
increase of Treg in peripheral
blood up to 25-30%, while
proinflammatory Th17 and Th1
cellsshowedadecreasingtrendin
healthyindividuals(Fig.C)
D
B
E
C
Base
d14
F
D/E) Func)onal analysis of peripheral Treg via
Mixed Lymphocyte Reac)on (MLR) reveals an
slightly but not significant increase in Treg
supressive capacity aSer PA intake for 14 days in
healthy individuals. Fig. D) shows prolifera)on of
CFSE stained PBMC in coculture with unstained
Treg before (Base – black) and aSer 14d of PA
intake (d14 – red). Prolifera)on was measured by
FACSaSer3-5daysofcoculture.
F) Deep Immune-Phenotyping of
peripheral blood from healthy
individuals before and aSer PA
intake showed no significant
changes in specific lymphocyte
subgroups like all T cells (CD3+), T
helpercells(CD4+),cytotoxicTcells
(CD8+) natural killer cells (NK cells,
CD16+CD56+)andBcells(CD19+).
Conclusion: We report the first in vivo effect on T cell subsets of PA in humans. Our results underline the influence of short chain fa9y acid
Propionateonthesystemicimmuneresponseandmaybeincludedinadd-onregimeninaddi)ontoestablishedfirstlineMSdrugs.
Correspondence: Dr. Aiden Haghikia, Dept. of Neurology,
Ruhr-University Bochum, St. Josef-Hospital, Gudrunstr. 56, 44791 Bochum, Germany, [email protected]
The authors of this poster report no specific conflict of interest.
Resources: Haghikia et al. Immunity. 2015 Oct 20;43(4):817-29.
doi: 10.1016/j.immuni.2015.09.007.007.