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

Publication ,  Journal Article
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 in: PLoS One
2011

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.

Duke Scholars

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

10

Start / End Page

e25833

Location

United States

Related Subject Headings

  • Up-Regulation
  • Th17 Cells
  • Receptors, CCR2
  • Neutrophils
  • Neutrophil Infiltration
  • Monocytes
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice
  • Lymph Nodes
 

Citation

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Rampersad, R. R., Tarrant, T. K., Vallanat, C. T., Quintero-Matthews, T., Weeks, M. F., Esserman, D. A., … Liu, P. (2011). Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune arthritis. PLoS One, 6(10), e25833. https://doi.org/10.1371/journal.pone.0025833
Rampersad, Rishi R., Teresa K. Tarrant, Christopher T. Vallanat, Tatiana Quintero-Matthews, Michael F. Weeks, Denise A. Esserman, Jennifer Clark, et al. “Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune arthritis.PLoS One 6, no. 10 (2011): e25833. https://doi.org/10.1371/journal.pone.0025833.
Rampersad RR, Tarrant TK, Vallanat CT, Quintero-Matthews T, Weeks MF, Esserman DA, et al. Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune arthritis. PLoS One. 2011;6(10):e25833.
Rampersad, Rishi R., et al. “Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune arthritis.PLoS One, vol. 6, no. 10, 2011, p. e25833. Pubmed, doi:10.1371/journal.pone.0025833.
Rampersad RR, Tarrant TK, Vallanat CT, Quintero-Matthews T, Weeks MF, Esserman DA, Clark J, Di Padova F, Patel DD, Fong AM, Liu P. Enhanced Th17-cell responses render CCR2-deficient mice more susceptible for autoimmune arthritis. PLoS One. 2011;6(10):e25833.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

10

Start / End Page

e25833

Location

United States

Related Subject Headings

  • Up-Regulation
  • Th17 Cells
  • Receptors, CCR2
  • Neutrophils
  • Neutrophil Infiltration
  • Monocytes
  • Mice, Inbred DBA
  • Mice, Inbred C57BL
  • Mice
  • Lymph Nodes