Mice deficient for CCR6 fail to control chronic experimental autoimmune encephalomyelitis.
Chemokines are a superfamily of chemotactic cytokines that play an important role in leukocyte trafficking and have been implicated as functional mediators of immunopathology in experimental autoimmune encephalomyelitis (EAE). In the present study, we investigated the role of the CCL20 receptor, CCR6, in chronic EAE. After immunization with myelin oligodendrocyte glycoprotein 35-55 in CFA, CCR6(-/-) mice developed a significantly more severe chronic EAE as compared to wild type immunized animals. CCR6 expression was not required by T cells to induce EAE. Measurement of peripheral T cell responses showed differences in IFN-gamma and IL-17 responses between CCR6(-/-) and wild type mice. At the time when CCR6(-/-) mice showed significantly more severe chronic EAE there was a significant decrease in PD-L1-expressing mDC in the spleens and no differences in Foxp3 Treg. Furthermore, add back of mDC with increased PD-L1 expression to CCR6(-/-) mice reduced the severe chronic EAE disease phase to that of wild type controls. The results suggest a role for CCR6-expressing PDL1(+) mDC in regulating EAE progression.
Elhofy
Adam
A
Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago IL 60611, USA.
Depaolo
R William
RW
Lira
Sergio A
SA
Lukacs
Nicholas W
NW
Karpus
William J
WJ
D000818:Animals; D018122:B7-1 Antigen / Q000378:metabolism*; D060890:B7-H1 Antigen; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007108:Immune Tolerance / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010455:Peptides / Q000378:metabolism*; D054399:Receptors, CCR6 / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498126:CCR6 protein, mouse; C498919:Cd274 protein, mouse; D020381:Interleukin-17; D008562:Membrane Glycoproteins; D010455:Peptides; D054399:Receptors, CCR6; D007371:Interferon-gamma