• Jana Janovska Riga Stradins University, Latvia
  • Julia Voicehovska Riga Stradins University, Latvia
  • Regina Kleina Riga Stradins University, Latvia
  • Janis Kisis Riga Stradins University, Latvia
  • Raimonds Karls Riga Stradins University, Latvia
  • Olga Zubova Riga Stradins University, Latvia
  • Sergejs Babikovs Riga Stradins University, Latvia
Keywords: Dendritic cells, Langerhans cells, metabolic syndrome, vitamin D deficiency


Vitamin D has immunomodulatory properties, which influence the immune system through a number of mechanisms, including the activation of dendritic cells (DCs). Langerhans cells (LCs) are dendritic cells in epidermis and belong to the skin immune system. DCs are professional antigen-presenting cells playing a major role in the induction of immune responses by activating native T-cells. In literature, there are no reports regarding the influence of vitamin D on DCs in patients with metabolic syndrome (MS).  Thus, the aim of this study is to explore potential immunomodulatory activity of vitamin D on LCs in case of metabolic syndrome. 

In this study, we have conducted an analysis on a group of patients, both male and female, diagnosed with metabolic syndrome between the age of 40 and 55. Patients’ clinical examinations, measurement of blood pressure, and waist circumference were conducted. Blood biochemical analyses (cholesterol, HDL, LDL, vitamin D level, etc.) were also determined. Full-thickness circular 4-mm Punch biopsies were taken from 49 patients. Specimens were stained with haematoxylin and eosin, as well as immunohistochemistry using a transmembrane CD1a Langerhans’ cells marker was parformed by DakoCytomation EnVision method. 

The average age of patients is 43 years, and mean waist circumference is 95 cm. Total cholesterol is 5.5 mmol/l, LDL is 2.3 mmol/l, and average 25-hydroxyvitamin D is 27.0 ng/ml.  In the skin conditioned with MS and low vitamin D level, evidence of perivascular accumulation of LCs in papillary dermis is observed, as well as a diffusion of mild interstitial cluster of LCs in some cases.  In epidermis activity, the amount and filling of Birbeck’s granules is changed in cases of 25-hydroxyvitamin D deficiency.  In patients with low 25-hydroxyvitamin D level, an average LC quantity in one field of vision is higher in comparison to those who have normal amount of 25-hydroxyvitamin D.  Therefore, it is necessary to further investigate vitamin D activity on LCs in cases of metabolic syndrome in order to determine interactions with lymphocytes, plasma cells, and mast cells as a part of the skin immune system.


Alberti, M., & Zimmet, P. (2006). Metabolic syndrome—a new world–wide definition. A consensus statement from the International Diabetes Federation. Diabetic Medicine, 23, 469-480

Austyn, J. M. (1987). Lymphoid dendritic cells. Immunology, 62, 161-170.

Banchereau, J., & Steinman, R. M. (1998). Dendritic cells and the control of immunity (Review). Nature, 392, 245–252.

Bikle, D. D. (2004). Vitamin D regulated keratinocyte differentiation. Journal of Cellular Biochemistry, 92, 436– 444.

Bikle, D. D., Chang, S., Crumrine, D., Elalieh, H., Man, M. Q., Dardenne, O., Xie, Z., Arnaud, R. S., Feingold, K., & Elias, P. M. (2004). Mice lacking 25OHD 1alpha- hydroxylase demonstrate decreased epidermal differentiation and barrier function. Journal of Steroid Biochemistry and Molecular Biology, 90(5), 347–353.

Dixon, K. M. Tongkao-On, W., Sequeira, V. B., Carter, S. E., Song, E. J., Rybchyn, M. S., Gordon-Thomson, C., & Mason, R. S. (2013). Vitamin D and Death by Sunshine, International Journal of Molecular Sciences, 14(1), 1964–1977.

Elbe, A., Tschachler, E., Steiner, G., Binder, A., Wolff, K., & Stingl, G. (1989). Maturational steps of bone marrow-derived dendritic murine epidermal cells. Phenotypic and functional studies on Langerhans cells and Thy-1+ dendritic epidermal cells in the perinatal period. The Journal of Immunology, 143, 2431–2438.

International Diabetes Federation (2006). The IDF consensus worldwide definition of the metabolic syndrome, 7-11.

Janovska, J., Kisis, J., Voicehovska, J., Kleina, R., Sherbuks, M., Karls, R., & Orlikovs, G. (2013) Pilot study of early skin changes due to metabolic syndrome. Collection of Scientific Papers 2012, 11-17. Riga: RSU.

Kissenpfennig, A., & Malissen, B. (2006) Langerhans cells–revisiting the paradigm using genetically engineered mice (Review). Trends Immunol, 27, 132–139.

Lee, C. H., & Wu, S. B. (2013, March 20). Molecular mechanisms of UV–induced apoptosis and its effects on skin residential cells: the implication in UV–based phototherapy. International Journal of Molecular Sciences, 14(3), 6414–6435.

Mardones, F., Zemelman, V., Sazunic, I., Morales, C., Palma, K., & Vargas, M.. (2009) CD1a+ Langerhans cells in the peritumoral epidermis of Basal cell carcinoma. Actas Dermo-sifiliograficas, 100, 700-705.

Oda,Y., Sihlbom, C., Chalkley, R. J., Huang, L., Rachez, C., Chang, C. P., Burlingame, A. L., Freedman, L. P., & Bikle, D. D. (2004). Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in VDR transactivation during keratinocyte differentiation. Journal of Steroid Biochemistry and Molecular Biology, 90(5), 273–276.

Potapova, O. V., Luzgina, N. G., & Shkurupiy, V. A. (2008). Immunomorphological study of Langerhans cells in skin of patients with atopic dermatitis. Bulletin of Experimental Biology and Medicine, 146(6), 809-811.

Prignano, F., Gerlini, G., Fossombroni, V., Pimpinelli, N., Giannotti, B., Nestle, F. O., & Romagnoli, P. (2001). Control of the differentiation state and function of human epidermal Langerhans cells by cytokines in vitro. Journal of European Academy of Dermatology and Venereology, 15(5), 433-440.

Prosser, D. E., & Jones, G. (2004). Enzymes involved in the activation and inactivation of vitamin D. Trends in Biochemical Sciences, 29, 664–673.

Santos, I., Mello, R. J., Santos, I. B., & Santos, R. A.. (2010). Quantitative study of Langerhans cells in basal cell carcinoma with higher or lower potential of local aggressiveness. Anais Brasileiros de Dermatologia, 85(2), 165-171.

Schaerli, P., Willimann, K., Ebert, L. M., Walz, A., & Moser, B. (2005) Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation. Immunity, 23: 331–342.

Schauber, J., & Gallo, R. L. (2009). Antimicrobial peptides and the skin immune defense system. Journal of Allergy and Clinical Immunology, 124(3), 261–266.

Schauber, J., Dorschner, R. A., Yamasaki, K., Brouha, B., & Gallo, R. L. (2006). Control of the innate epithelial antimicrobial response is cell-type specific and dependent on relevant microenvironmental stimuli. Immunology, 118, 509–519.

Schmidt, S. V., Nino-Castro, A. C., & Schultze, J. L. (2012). Regulatory dendritic cells: there is more than just immune activation. Frontiers in Immunology, 3, 274.

Toebak, M. J., & Gibbs, S. (2009). Dendritic cells: biology of the skin. Contact Dermatitis, 60, 2–20.

Tony, C., & Ronald, J. (1994) The normal Langerhans cell and the LCH cells, British Journal of Cancer, 70.

Van Etten, E., & Mathieu, C. (2005). Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. Journal of Steroid Biochemistry and Molecular Biology, 97, 93–101.

Van Wilsem, E. J. G., Breve, J., Kleijmeer, M., & Kraal, G. (1994) Antigen-Bearing Langerhans cells in skin draining lymph nodes: phenotype and kinetics of migration. Journal of Investigative Dermatology, 217–220.

Yim, S., Dhawan, P., Ragunath, C., Christakos, S., & Diamond, G. (2007). Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3). Journal of Cystic Fibrosis, 6, 403–410.

Zhang, R., &, Naughton, D. P. (2010). Vitamin D in health and disease: Current perspectives. Nutrition Journal, 9, 65.