GPR15 + T cells are Th17 like, increased in smokers and associated with multiple sclerosis
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GPR15 + T cells are Th17 like, increased in smokers and associated with multiple sclerosis. / Ammitzbøll, Cecilie; von Essen, Marina R.; Börnsen, Lars; Petersen, Eva Rosa; McWilliam, Oskar; Ratzer, Rikke; Romme Christensen, Jeppe; Oturai, Annette B.; Søndergaard, Helle B.; Sellebjerg, Finn.
I: Journal of Autoimmunity, Bind 97, 2019, s. 114-121.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - GPR15 + T cells are Th17 like, increased in smokers and associated with multiple sclerosis
AU - Ammitzbøll, Cecilie
AU - von Essen, Marina R.
AU - Börnsen, Lars
AU - Petersen, Eva Rosa
AU - McWilliam, Oskar
AU - Ratzer, Rikke
AU - Romme Christensen, Jeppe
AU - Oturai, Annette B.
AU - Søndergaard, Helle B.
AU - Sellebjerg, Finn
PY - 2019
Y1 - 2019
N2 - Smoking is a risk factor for the development and progression of multiple sclerosis (MS); however, the pathogenic effects of smoking are poorly understood. We studied the smoking-associated chemokine receptor-like molecule GPR15 in relation to relapsing-remitting MS (RRMS). Using microarray analyses and qPCR we found elevated GPR15 in blood cells from smokers, and increased GPR15 expression in RRMS. By flow cytometry we detected increased frequencies of GPR15 expressing T and B cells in smokers, but no difference between patients with RRMS and healthy controls. However, after cell culture with the autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein, frequencies of MBP-reactive and non-proliferating GPR15 + CD4 + T cells were increased in patients with RRMS compared with healthy controls. GPR15 + CD4 + T cells produced IL-17 and were enriched in the cerebrospinal fluid (CSF). Furthermore, in the CSF of patients with RRMS, GPR15 + T cells were associated with CCR6 + CXCR3 + /CCR6 − CXCR3 + phenotypes and correlated positively with concentrations of the newly identified GPR15-ligand (GPR15L), myelin degradation and disability. In conclusion, we have identified a proinflammatory cell type linking smoking with pathogenic immune cell functions in RRMS.
AB - Smoking is a risk factor for the development and progression of multiple sclerosis (MS); however, the pathogenic effects of smoking are poorly understood. We studied the smoking-associated chemokine receptor-like molecule GPR15 in relation to relapsing-remitting MS (RRMS). Using microarray analyses and qPCR we found elevated GPR15 in blood cells from smokers, and increased GPR15 expression in RRMS. By flow cytometry we detected increased frequencies of GPR15 expressing T and B cells in smokers, but no difference between patients with RRMS and healthy controls. However, after cell culture with the autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein, frequencies of MBP-reactive and non-proliferating GPR15 + CD4 + T cells were increased in patients with RRMS compared with healthy controls. GPR15 + CD4 + T cells produced IL-17 and were enriched in the cerebrospinal fluid (CSF). Furthermore, in the CSF of patients with RRMS, GPR15 + T cells were associated with CCR6 + CXCR3 + /CCR6 − CXCR3 + phenotypes and correlated positively with concentrations of the newly identified GPR15-ligand (GPR15L), myelin degradation and disability. In conclusion, we have identified a proinflammatory cell type linking smoking with pathogenic immune cell functions in RRMS.
KW - CD4
KW - CSF
KW - GPR15
KW - Multiple sclerosis
KW - RRMS
KW - Smoking
U2 - 10.1016/j.jaut.2018.09.005
DO - 10.1016/j.jaut.2018.09.005
M3 - Journal article
C2 - 30245027
AN - SCOPUS:85060587980
VL - 97
SP - 114
EP - 121
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
ER -
ID: 241101975