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@ARTICLE{Kraus:212548,
author = {F. V. Kraus and S. Keck and K. Klika$^*$ and J. Graf and R.
A. Carvalho and H.-M. Lorenz and M. M. Souto-Carneiro},
title = {{R}eduction of pro-inflammatory effector functions through
remodeling of fatty acid metabolism in {CD}8+ {T}-cells from
rheumatoid arthritis patients.},
journal = {Arthritis $\&$ rheumatology},
volume = {75},
number = {7},
issn = {2326-5191},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DKFZ-2023-00233},
pages = {1098-1109},
year = {2023},
note = {2023 Jul;75(7):1098-1109},
abstract = {Rheumatoid arthritis (RA) CD8+ T-cells (CD8) maintain their
effector pro-inflammatory phenotype by changing their
metabolism towards aerobic glycolysis. However, their
massive energetic and biosynthetic needs may require
additional substrates other than glucose. Since systemic
alterations in lipid metabolism have been reported in RA
patients, we explored the role of fatty acid (FA) metabolism
in CD8 to identify potential targets to curb their
pro-inflammatory potential.The expression of FA
metabolism-related genes was analyzed for total and
CD8-subsets in the data of RA patients and healthy controls
retrieved from the gene expression omnibus database.
Functional assays were performed on peripheral-blood CD8
isolated from RA (n=31), PsA (n=26), and SpA (n=21) patients
under different therapies (DMARD, biologicals, and JAK
inhibitors) and controls (n=13). We quantified the
expression of FA transporters, lipid uptake, intracellular
FA content, cytokine production, activation, proliferation,
and capacity to inhibit tumor cell growth, either with or
without FA metabolism inhibitors.The CD8 gene expression
profile of FA metabolism-related genes was significantly
different between untreated RA patients and controls. RA
patients with a good clinical response after 6 months MTX
therapy significantly increased the expression of FA
metabolism-related genes. Cell-surface expression of FA
transporters FABP4 and GPR84 and FA uptake was higher in
effector and memory CD8 of RA patients than for controls. In
vitro blockade of FA metabolism significantly impaired CD8
effector functions.RA CD8 present an altered FA metabolism
which can provide potential therapeutic targets to control
the pro-inflammatory profile. Particularly, therapies
directed against the transport and oxidation of free FA.},
cin = {W160},
ddc = {610},
cid = {I:(DE-He78)W160-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36704915},
doi = {10.1002/art.42456},
url = {https://inrepo02.dkfz.de/record/212548},
}