Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune arthritis.

Journal Article (Journal Article)

CCR2 is considered a proinflammatory mediator in many inflammatory diseases such as rheumatoid arthritis. However, mice lacking CCR2 develop exacerbated collagen-induced arthritis. To explore the underlying mechanism, we investigated whether autoimmune-associated Th17 cells were involved in the pathogenesis of the severe phenotype of autoimmune arthritis. We found that Th17 cells were expanded approximately 3-fold in the draining lymph nodes of immunized CCR2(-/-) mice compared to WT controls (p = 0.017), whereas the number of Th1 cells and regulatory T cells are similar between these two groups of mice. Consistently, levels of the Th17 cell cytokine IL-17A and Th17 cell-associated cytokines, IL-6 and IL-1β were approximately 2-6-fold elevated in the serum and 22-28-fold increased in the arthritic joints in CCR2(-/-) mice compared to WT mice (p = 0.04, 0.0004, and 0.01 for IL-17, IL-6, and IL-1β, respectively, in the serum and p = 0.009, 0.02, and 0.02 in the joints). Furthermore, type II collagen-specific antibodies were significantly increased, which was accompanied by B cell and neutrophil expansion in CCR2(-/-) mice. Finally, treatment with an anti-IL-17A antibody modestly reduced the disease severity in CCR2(-/-) mice. Therefore, we conclude that while we detect markedly enhanced Th17-cell responses in collagen-induced arthritis in CCR2-deficient mice and IL-17A blockade does have an ameliorating effect, factors additional to Th17 cells and IL-17A also contribute to the severe autoimmune arthritis seen in CCR2 deficiency. CCR2 may have a protective role in the pathogenesis of autoimmune arthritis. Our data that monocytes were missing from the spleen while remained abundant in the bone marrow and joints of immunized CCR2(-/-) mice suggest that there is a potential link between CCR2-expressing monocytes and Th17 cells during autoimmunity.

Full Text

Duke Authors

Cited Authors

  • Rampersad, RR; Tarrant, TK; Vallanat, CT; Quintero-Matthews, T; Weeks, MF; Esserman, DA; Clark, J; Di Padova, F; Patel, DD; Fong, AM; Liu, P

Published Date

  • 2011

Published In

Volume / Issue

  • 6 / 10

Start / End Page

  • e25833 -

PubMed ID

  • 21991368

Pubmed Central ID

  • PMC3186765

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0025833


  • eng

Conference Location

  • United States