Prof. Dr. Margitta Worm

Charité – Universitätsmedizin Berlin
Klinik für Dermatologie und Allergologie
Charitéplatz 1
10117 Berlin

Tel. +49 (0) 30 450 518105
margitta.worm@charite.de

Dr. Arndt Guido Heine

Charité – Universitätsmedizin Berlin
Klinik für Dermatologie und Allergologie
Charitéplatz 1
10117 Berlin

Tel. +49 (0) 30 450 618305
guido.heine@charite.de

Project summary:

Regulation of B cell differentiation by vitamin A and D

Vitamin D and A both are potent regulators of B cell function. Both vitamins are acting by receptors that can interact with each other. Little is known about how these receptors act on B cell differentiation. We have demonstrated previously that B cells can synthesize the active vitamin D metabolite (calcitriol) from provitamin D (25-hydroxyvitamin D) and that active vitamin D directly and selectively blocks the production of IgE, the key effector molecule in allergy, and enhances expression of interleukin-10 (IL-10), a cytokine that can act anti-inflammatory. Likewise, vitamin A has been shown to regulate transforming growth factor-ß (TGF-ß) expression, which can act anti-inflammatory and to promote IgA production. Thus, vitamin D and A in B cells target two major arms of physiological regulation of immune responses, namely antibody production and cytokine expression. However, the precise molecular mechanisms of gene regulation by the vitamins are not clear. In this project we aim to determine how the metabolism of vitamin D and A and the respective signaling develop during B cell differentiation. By identifying specific target genes of both receptors, we aim to determine the role of B cells during protective and pathogenic immune responses. In perspective, promising protocols will be translated into clinical application.

Publications P 19:

Hallau, J., Hamann, L., Schumann, R.R., Worm, M., and Heine, G. (2016). A Promoter Polymorphism of the Vitamin D Metabolism Gene Cyp24a1 is Associated with Severe Atopic Dermatitis in Adults. Acta Derm Venereol 96, 169-172.

Kumari, V., Timm, K., Kühl, A.A., Heine, G., and Worm, M. (2016). Impact of systemic alitretinoin treatment on skin barrier gene and protein expression in patients with chronic hand eczema. Br J Dermatol doi: 10.1111/bjd.14921.

Babina M, Guhl S, Motakis E, Artuc M, Hazzan T, Worm M, Forrest AR, Zuberbier T. (2015) Retinoic acid potentiates inflammatory cytokines in human mast cells: identification of mast cells as prominent constituents of the skin retinoid network. Mol Cell Endocrinol 406, 49-59.

Heine, G., Drozdenko, G., Grün, J.R., Chang, H.D., Radbruch, A., and Worm, M. (2014). Autocrine IL-10 promotes human B-cell differentiation into IgM- or IgG-secreting plasmablasts. Eur J Immunol 44, 1615-21.

Heine, G., Tabeling, C., Hartmann, B., Gonzalez Calera, C.R., Kuhl, A.A., Lindner, J., Radbruch, A., Witzenrath, M., and Worm, M. (2014). 25-hydroxvitamin D3 promotes the long-term effect of specific immunotherapy in a murine allergy model. J Immunol 193, 1017-1023.

Schindler, M., Drozdenko, G., Kuhl, A.A., and Worm, M. (2014). Immunomodulation in patients with chronic hand eczema treated with oral alitretinoin. Int Arch Allergy Immunol 165, 18-26.