Article Text

other Versions

PDF
Blockade of CD40-CD40 ligand interactions attenuates skin fibrosis and autoimmunity in the tight-skin mouse
  1. Kazuhiro Komura (komuraka{at}mac.com)
  1. Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
    1. Manabu Fujimoto (mfujimoto{at}derma.m.kanazawa-u.ac.jp)
    1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
      1. Koichi Yanaba (yanaba{at}rf6.so-net.ne.jp)
      1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
        1. Takashi Matsushita (takashi.matsushita{at}mac.com)
        1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
          1. Yukiyo Matsushita (matusita{at}kanazawa-shaho.com)
          1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
            1. Mayuka Horikawa (mayuka.horikawa{at}duke.edu)
            1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
              1. Fumihide Ogawa (fogawa{at}nagasaki-u.ac.jp)
              1. Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
                1. Kazuhiro Shimizu (kashimizu{at}nagasaki-u.ac.jp)
                1. Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Japan
                  1. Minoru Hasegawa (minoruha{at}derma.m.kanazawa-u.ac.jp)
                  1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
                    1. Kazuhiko Takehara (takehara{at}med.m.kanazawa-u.ac.jp)
                    1. Department of Dermatology, Kanazawa University Graduate School of Medical Science, Japan
                      1. Shinichi Sato (s-sato{at}nagasaki-u.ac.jp)
                      1. Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Japan

                        Abstract

                        Objective: To assess the association of CD40/CD40 ligand (CD40L) interactions with the development of skin fibrosis and autoimmunity in tight-skin (TSK/+) mouse, which is a mouse model for human systemic sclerosis.

                        Methods: Newly born TSK/+ mice were treated by murine anti-CD40L monoclonal antibody (Ab, 100 μg i.p. weekly). Hypodermal thickness of 8-week-old female mice, which was defined as the thickness of a subcutaneous loose connective tissue layer beneath the panniculus carnosus, was measured under a light microscope. All skin sections were taken from the para-midline, upper back region. Serum anti-topoisomerase I autoantibody levels, serum immunoglobulin levels, and plasma soluble CD40L levels were determined by enzyme linked immunosorbent assay. For analysis of lymphocytes surface molecules, single-cell suspensions of lymphocytes were stained by monoclonal Abs. Proliferation of TSK/+ B cells and fibroblasts to anti-CD40 Ab was assessed by the uptake of [3H]-labeled thymidine and BrdU, respectively.

                        Results: The blockade of CD40/CD40L interactions by anti-CD40L monoclonal Ab significantly reduced cutaneous fibrosis (65%) and anti-topisomerase I autoantibody in TSK/+ mice. Anti-CD40L monoclonal Ab also normalized B lymphocyte abnormal activation in TSK/+ mice, demonstrated by hyper-γ-globulinemia. Furthermore, augmented CD40/CD40L interactions in TSK/+ mice were suggested by up-regulated expression of CD40L on CD4+ T cells, elevated plasma soluble CD40L levels. The hyperresponsiveness to CD40 stimulation was also observed in TSK/+ B cells and fibroblasts.

                        Conclusion: Cutaneous fibrosis and autoimmunity in TSK/+ mice are closely correlated with CD40/CD40L interactions

                        • CD40L
                        • autoimmunity
                        • fibrosis
                        • systemic sclerosis
                        • therapy

                        Statistics from Altmetric.com

                        Request permissions

                        If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.