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
Prof. Dr. Arndt Guido Heine
Charité – Universitätsmedizin Berlin
Klinik für Dermatologie und Allergologie
Charitéplatz 1
10117 Berlin
Tel. +49 (0) 30 450 618305
gheine@dermatology.uni-kiel.de
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.
Heine, G., Francuzik, W., Doelle-Bierke, S., Drozdenko, G., Frischbutter, S., Schumacher, N., Radbruch, A. and Worm, M. (2020). Immunomodulation of high-dose vitamin D supplementation during allergen specific immunotherapy. Allergy doi: 10.1111/all.14541.
Treptow, S., Grün, J., Scholz, J., Radbruch, A., Heine, G., and Worm, M. (2020). 9-cis retinoic acid and 1.25-dihydroxyvitamin D3 drive differentiation into IgA+ secreting plasmablasts in human naïve B cells. Eur. J. Immunol. doi: 10.1002/eji.202048557.
Scholz, F., Heinrich, F.R., Heinz, G.A., Hutloff, A., Worm, M., and Heine, G. (2020). Retinoic acid receptor alpha promotes lymphocyte-specific differentiation into antibody-secreting cells and follicular T helper cells. Allergy in press.
Worm, M., Heine, G., Radbruch, A., et al. (2018). Immunomodulation by vitamin D. Allergologie Select 2, 62-66.
Heine, G., Hollstein, T., Treptow, S., Radbruch, A., and Worm, M. (2018). 9-cis retinoic acid modulates the type I allergic immune response. J. Allergy Clin. Immunol. 2, 650-658.e5.
Lindner, J., Rausch, S., Treptow, S., Geldmeyer-Hilt, K., Krause, T., St-Arnaud, R., Arabian, A., Radbruch, A., Hartmann, S., Worm, M., and Heine, G. (2017). Endogenous Calcitriol Synthesis Controls the Humoral IgE Response in Mice. J. Immunol. 199, 3952-3958.
Wylon, K., Drozdenko, G., Krannich, A., Heine, G., Dölle, S., and Worm, M. (2017). Pharmacokinetic Evaluation of a Single Intramuscular High Dose versus an Oral Long-Term Supplementation of Cholecalciferol. PLoS One 12, e0169620. doi: 10.1371/journal.pone.0169620.
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.