Funding sources This work was supported by a grant from Maruho Co. Ltd.
CLINICAL AND LABORATORY INVESTIGATIONS
Heat-killed bacillus Calmette–Guérin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells
Article first published online: 4 APR 2012
© 2011 The Authors. BJD © 2011 British Association of Dermatologists
British Journal of Dermatology
Volume 166, Issue 5, pages 953–963, May 2012
How to Cite
Kakeda, M., Yamanaka, K., Kitagawa, H., Tsuda, K., Akeda, T., Kurokawa, I., Gabazza, E.C. and Mizutani, H. (2012), Heat-killed bacillus Calmette–Guérin and Mycobacterium kansasii antigen 85B combined vaccination ameliorates dermatitis in a mouse model of atopic dermatitis by inducing regulatory T cells. British Journal of Dermatology, 166: 953–963. doi: 10.1111/j.1365-2133.2011.10763.x
Conflicts of interest H.M. and K.Y. have received support by Grant-in-Aids for Scientific Research from the Japan Ministry of Education, Culture, Sports, Science and Technology.
- Issue published online: 23 APR 2012
- Article first published online: 4 APR 2012
- Accepted manuscript online: 2 DEC 2011 09:42AM EST
- Accepted for publication 23 November 2011
Background Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by dominant T-helper (Th) 2 cytokine response. Bacillus Calmette–Guérin (BCG) has been used for preventing tuberculosis, and is regarded as a strong Th1 cytokine inducer. Antigen (Ag) 85B is a secretory protein present in Mycobacterium species that induces Th1 cytokine production.
Objectives We investigated the effects of combined vaccination of heat-killed BCG (hkBCG) and Mycobacterium kansasii Ag85B in an AD mouse model.
Methods For the AD model, keratin 14 promoter-derived caspase-1 overexpressing mice (KCASP1Tg) were used. The mice received a combination therapy of hkBCG at age 3 weeks and Ag85B twice weekly for 11 weeks from the 4th week; Ag85B monotherapy from the 4th week; hkBCG monotherapy at the 3rd week; or control saline. Areas of skin lesions, cytokine mRNA expression and serum interleukin (IL)-18 and immunoglobulin (Ig) E levels were analysed. Inducible Foxp3+ regulatory T cells (iTreg), IL-10-producing T cells (Tr1), and interferon (IFN)-γ/IL-4/IL-17-producing T cells were evaluated in the spleen.
Results Saline-treated mice and hkBCG monotherapy mice spontaneously developed severe dermatitis. However, combined therapy with hkBCG and Ag85B significantly suppressed the development of skin lesions and mast cell infiltrations. Elevations of the serum IgE and IL-18 levels were significantly suppressed with combined therapy. Mice treated with hkBCG and Ag85B had a normal number of iTreg in the spleen, and decreased number of both IL-4- and IL-17-producing CD4+ T cells. The effect of Ag85B monotherapy was limited.
Conclusions Combined vaccination with hkBCG and Ag85B decreases AD skin lesions by inducing regulatory T cells, suggesting that this vaccination is a potent and novel therapeutic strategy for AD.