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

Autor: Michael F. Weeks, Denise Esserman, Dhavalkumar D. Patel, Rishi R. Rampersad, Teresa K. Tarrant, Franco Di Padova, Tatiana Quintero-Matthews, Jennifer J.J. Clark, Alan M. Fong, Peng Liu, Christopher T. Vallanat
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Neutrophils
medicine.medical_treatment
animal diseases
Arthritis
lcsh:Medicine
Autoimmunity
medicine.disease_cause
Monocytes
Epitopes
Mice
0302 clinical medicine
Bone Marrow
lcsh:Science
0303 health sciences
B-Lymphocytes
Multidisciplinary
T Cells
Interleukin-17
hemic and immune systems
3. Good health
Up-Regulation
Cytokine
medicine.anatomical_structure
Neutrophil Infiltration
Mice
Inbred DBA
Rheumatoid arthritis
Cytokines
Medicine
Interleukin 17
Research Article
Receptors
CCR2
Immune Cells
Immunology
Rheumatoid Arthritis
Antibodies
Proinflammatory cytokine
Autoimmune Diseases
03 medical and health sciences
Rheumatology
parasitic diseases
medicine
Animals
Biology
B cell
030304 developmental biology
Autoantibodies
Cell Proliferation
Inflammation
business.industry
lcsh:R
Autoantibody
Immunity
medicine.disease
Arthritis
Experimental
Mice
Inbred C57BL
Immune System
Th17 Cells
Immunization
Joints
lcsh:Q
Lymph Nodes
business
030215 immunology
Zdroj: PLoS ONE, Vol 6, Iss 10, p e25833 (2011)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: