OBJECTIVE: Inducible costimulator (ICOS)-ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)-induced arthritis (PGIA). METHODS: PGIA was initiated by immunizing wild-type and ICOSL-deficient (ICOSL(-/-) ) or B cell-specific ICOSL(-/-) chimeric BALB/c mice with human PG in adjuvant. The onset and severity of arthritis were monitored over time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured in vitro after the cells were restimulated with PG. Germinal center (GC) B cells, plasma cells, Tfh cells, and Treg cells were identified by staining with specific antibodies. RESULTS: Arthritis progression was completely inhibited in both ICOSL(-/-) mice and B cell-specific ICOSL(-/-) chimeric mice. Production of the Teff cell-produced cytokines interferon-γ and interleukin-17 (IL-17) and the antiinflammatory cytokine IL-4 was suppressed. The reduced percentages of GCs and Tfh cells and the decreased production of IL-21 correlated with a decrease in the anti-mouse PG antibody response. However, the percentage of plasma cells was not reduced despite a reduction in IgG responses. CONCLUSION: These data indicate that the signals provided by ICOSL-expressing B cells to Teff cells and Tfh cells are necessary for the development of arthritis. Thus, therapeutic blockade of ICOSL-ICOS interactions may be an effective strategy for the treatment of rheumatoid arthritis.
OBJECTIVE:Inducible costimulator (ICOS)-ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)-induced arthritis (PGIA). METHODS: PGIA was initiated by immunizing wild-type and ICOSL-deficient (ICOSL(-/-) ) or B cell-specific ICOSL(-/-) chimeric BALB/c mice with human PG in adjuvant. The onset and severity of arthritis were monitored over time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured in vitro after the cells were restimulated with PG. Germinal center (GC) B cells, plasma cells, Tfh cells, and Treg cells were identified by staining with specific antibodies. RESULTS:Arthritis progression was completely inhibited in both ICOSL(-/-) mice and B cell-specific ICOSL(-/-) chimeric mice. Production of the Teff cell-produced cytokines interferon-γ and interleukin-17 (IL-17) and the antiinflammatory cytokine IL-4 was suppressed. The reduced percentages of GCs and Tfh cells and the decreased production of IL-21 correlated with a decrease in the anti-mouse PG antibody response. However, the percentage of plasma cells was not reduced despite a reduction in IgG responses. CONCLUSION: These data indicate that the signals provided by ICOSL-expressing B cells to Teff cells and Tfh cells are necessary for the development of arthritis. Thus, therapeutic blockade of ICOSL-ICOS interactions may be an effective strategy for the treatment of rheumatoid arthritis.
Authors: Eden Kleiman; Daria Salyakina; Magali De Heusch; Kristen L Hoek; Joan M Llanes; Iris Castro; Jacqueline A Wright; Emily S Clark; Derek M Dykxhoorn; Enrico Capobianco; Akiko Takeda; Jean-Christophe Renauld; Wasif N Khan Journal: Front Immunol Date: 2015-02-11 Impact factor: 7.561
Authors: Sung-Wook Hong; Eunju O; Jun Young Lee; Minji Lee; Daehee Han; Hyun-Ja Ko; Jonathan Sprent; Charles D Surh; Kwang Soon Kim Journal: Sci Adv Date: 2019-05-22 Impact factor: 14.136
Authors: Adela Navrátilová; Lucie Andrés Cerezo; Hana Hulejová; Viktor Bečvář; Michal Tomčík; Martin Komarc; David Veigl; Dana Tegzová; Jakub Závada; Marta Olejárová; Karel Pavelka; Jiří Vencovský; Ladislav Šenolt Journal: Front Immunol Date: 2021-10-21 Impact factor: 8.786