The chemokine receptor CCR7 and its ligands CCL19 and CCL21 guide the homing and positioning of dendritic and T cells in lymphoid organs, thereby contributing to several aspects of adaptive immunity and immune tolerance. In the present study, we investigated the role of CCR7 in the pathogenesis of collagen-induced arthritis (CIA). By using a novel anti-human CCR7 antibody and humanized CCR7 mice, we evaluated CCR7 as a target in this autoimmune model of rheumatoid arthritis (RA). Ccr7-deficient mice were completely resistant to CIA and presented severely impaired antibody responses to collagen II (CII). Selective CCR7 expression on dendritic cells restored arthritis severity and anti-CII antibody titers. Prophylactic and therapeutic treatment of humanized CCR7 mice with anti-human CCR7 mAb 8H3-16A12 led to complete resistance to CIA and halted CIA progression, respectively. Our data demonstrate that CCR7 signaling is essential for the induction of CIA and identify CCR7 as a potential therapeutic target in RA.
机构:
Univ Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Mahomva, Chengetai R.
Smith, Kristine A.
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Univ Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Smith, Kristine A.
Minkah, Prince A. B.
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Univ Utah, Coll Pharm, Dept Mol Pharmaceut, Salt Lake City, UT USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Minkah, Prince A. B.
Witt, Benjamin L.
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Univ Utah, Cytopathol Sect, Sch Med, Salt Lake City, UT USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Witt, Benjamin L.
Oakley, Gretchen M.
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Univ Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Oakley, Gretchen M.
Orlandi, Richard R.
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Univ Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Orlandi, Richard R.
Alt, Jeremiah A.
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Univ Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Univ Utah, Coll Pharm, Dept Mol Pharmaceut, Salt Lake City, UT USA
Univ Utah, Coll Pharm, Utah Ctr Nanomed, Salt Lake City, UT USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Alt, Jeremiah A.
Pulsipher, Abigail
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Univ Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
Univ Utah, Coll Pharm, Dept Mol Pharmaceut, Salt Lake City, UT USA
Univ Utah, Coll Pharm, Utah Ctr Nanomed, Salt Lake City, UT USAUniv Utah, Dept Otolaryngol Head & Neck Surg, Sch Med, 36 South Wasatch Dr, Salt Lake City, UT 84112 USA
机构:
Corporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Div Rheumatol, Philadelphia, PA 19104 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Sambamurthy, Nisha
Vu Nguyen
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机构:
Corporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Div Rheumatol, Philadelphia, PA 19104 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Vu Nguyen
Smalley, Ryan
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机构:
Corporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Smalley, Ryan
Xiao, Rui
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机构:
Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Xiao, Rui
Hankenson, Kurt
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机构:
Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USA
Univ Michigan, Sch Med, Dept Orthopaed Surg, Ann Arbor, MI USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Hankenson, Kurt
Gan, Justin
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Rush Univ, Med Ctr, Div Rheumatol, Chicago, IL 60612 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Gan, Justin
Miller, Rachel E.
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机构:
Rush Univ, Med Ctr, Div Rheumatol, Chicago, IL 60612 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Miller, Rachel E.
Malfait, Anne-Marie
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机构:
Rush Univ, Med Ctr, Div Rheumatol, Chicago, IL 60612 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Malfait, Anne-Marie
Dodge, George R.
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机构:
Corporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Dodge, George R.
Scanzello, Carla R.
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h-index: 0
机构:
Corporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Div Rheumatol, Philadelphia, PA 19104 USA
Univ Penn, Perelman Sch Med, Dept Orthoped Surg, Philadelphia, PA 19104 USACorporal Michael J Crescenz Dept Vet Affairs Med, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA