Protective effects of agonistic anti-4-1BB antibody on the development of imiquimod-induced psoriasis-like dermatitis in mice.
Agonistic anti-4-1BB antibodies (Abs) play a central role in immunomodulatory conditions that control the pathogenesis of immune-mediated autoimmune and allergic diseases. However, the effects of agonistic anti-4-1BB Abs have not been examined in an experimental mouse model of psoriasis. Therefore, we investigated the protective effects of agonistic anti-4-1BB Abs, using imiquimod (IMQ)-induced psoriasis-like dermatitis in mice, a condition histologically and clinically similar to human psoriasis. We found that administration of agonistic anti-4-1BB Abs (10mg/kg) significantly alleviated the severity of IMQ-induced psoriasis-like skin inflammation in mice, with reduced histologic symptoms, including inflammatory infiltration, parakeratosis, and hyperkeratosis. Subsequent analyses revealed that the production of Th17 cytokines (IL-17A and IL-23) in the serum and skin of IMQ-induced mice was significantly inhibited by agonistic anti-4-1BB Abs (10mg/kg), although Th1 cytokines (TNF-α and IFN-γ) were not. Moreover, administration of agonistic anti-4-1BB Abs (10mg/kg) induced a relative increase of CD4(+)FoxP3(+) regulatory T (Treg) cells in the spleen and draining lymph node (DLN). Taken together, our data provide evidence that agonistic anti-4-1BB Abs possesses immunosuppressive properties in IMQ-induced psoriasis-like skin inflammation, providing insight into the immunomodulatory effect of agonistic anti-4-1BB Abs for psoriasis immunotherapy.
Department of Pharmacy, College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongman-si, Gyeonggi-do 463-400, Republic of Korea.
Jung Ki
JK
Yoo
Department of Biological science, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Young-Kug
YK
Choo
Institute for Glycoscience, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
Dong Hoon
DH
Kwak
College of Medicine, Dongguk University, Goyang 410-773, Republic of Korea.
Jong Min
JM
Lee
Department of Biostatistics, Dongguk University, Goyang 410-773, Republic of Korea.
Chi-Yeon
CY
Lim
College of Korean Medicine, Dongguk University, Gyeongju 38066, Republic of Korea.
Ju-Hee
JH
Lee
Catholic Hematopoietic Stem Cell Bank, College of Medicine, The Catholic University of Korea, Seoul 137-701, Republic of Korea.
Mi-Young
MY
Park
College of Medicine, Dongguk University, Goyang 410-773, Republic of Korea. Electronic address: ctlkim@hanmail.net.
Chang-Hyun
CH
Kim
D000634:Aminoquinolines / Q000009:adverse effects*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D000077271:Imiquimod; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D020011:Protective Agents / Q000494:pharmacology*; D011565:Psoriasis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013163:Splenomegaly; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000819:agonists*
D000634:Aminoquinolines; D000911:Antibodies, Monoclonal; D016207:Cytokines; D018836:Inflammation Mediators; D020011:Protective Agents; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000077271:Imiquimod
4-1BB; Imiquimod; Psoriasis; Regulatory T cells; Th17 cytokines