title: Ustekinumab improves psoriasis without altering T cell cytokine production, differentiation, and T cell receptor repertoire diversity.
abstract: Ustekinumab is a fully human IgG1κ monoclonal antibody targeting interleukin (IL)-12/23 p40 subunit. The role of IL-12/23-mediated pathway in the mechanism of various inflammatory disorders especially psoriasis has been well recognized. Recently the long-term efficacy and safety of ustekinumab in patients with moderate-to-severe psoriasis has been evaluated in phase 2/3 clinical trials, and the results showed no significant risk for serious adverse effects, infections, or malignancies. Ustekinumab inhibits the function of the IL-12/23 p40 subunit, and therefore it is believed that inhibition of IL-12 p40 pathway decreases IFN-γ production. The major concern for the use of ustekinumab is the possibility of increased immunosuppression due to low IFN-γ production. However, the effects of ustekinumab on CD4(+) T cell function have not been fully investigated so far. In this study, we explored changes in cytokine production by memory CD4(+) T cells as well as in the differentiation of naïve T cells to helper T cell (Th) 1, Th2, or Th17 cells in psoriasis patients treated with ustekinumab. The effect of the treatment on T cell receptor repertoire diversity was also evaluated. The results showed that ustekinumab improves clinical manifestation in patients with psoriasis without affecting cytokine production in memory T cells, T cell maturation, or T cell receptor repertoire diversity. Although the number of patients is limited, the present study suggests that T cell immune response remains unaffected in psoriasis patients treated with ustekinumab.
authors.affiliation: Department of Dermatology, Mie University, Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Kenshiro
authors.initials: K
authors.lastname: Tsuda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Yamanaka
authors.forename: Makoto
authors.initials: M
authors.lastname: Kondo
authors.forename: Kimiko
authors.initials: K
authors.lastname: Matsubara
authors.forename: Ryogen
authors.initials: R
authors.lastname: Sasaki
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tomimoto
authors.forename: Esteban C
authors.initials: EC
authors.lastname: Gabazza
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Mizutani
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D000069549:Ustekinumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D011948:Receptors, Antigen, T-Cell; D000069549:Ustekinumab