In the mouse, cutaneous application of vitamin D3 results in a Th2-driven inflammation resembling atopic dermatitis. This response relies on Thymic Stromal Lymphopoietin (TSLP) production by keratinocytes and T cell orientation by TSLP-stimulated skin dendritic cells (DCs). Nevertheless, similar effects of vitamin D3 have not been confirmed thus far by in vitro models involving human skin.    
We have studied in human skin explants whether vitamin D3 analogs allow emigrating skin DCs to promote human Th2 responses. In line with a previous report, topical application of calcipotriol cream or calcitriol addition in the culture medium increased the rate of CD14+ DCs recovered after 3 days of culture. Using immunofluorescence microscopy of cultured skin and monocyte-derived dendritic cells (MonoDCs) stimulated with calcitriol, we showed that CD14 upregulation is a direct consequence of vitamin D3 exposure rather than an increased migration of CD14+ dermal DCs.
Skin-emigrating DCs were collected and cocultured with naïve CD4+ T cells from a different donor. This resulted in a clear orientation towards Th2 differentiation, for which CD14+ DCs appeared sufficient. Finally, we found that both analogs of vitamin D3 induced TSLP production by human skin. However, poor correlation between TSLP amounts and the Th2-driving capacity of skin DCs suggested a TSLP-independent effect. Of note, vitamin D3-stimulated MonoDCs also yielded strong Th2 differentiation in the absence of TSLP.
Therefore, our findings reveal possible TSLP-independent effects of vitamin D3 on T cell responses, which are currently under investigation. Altogether, we confirmed vitamin D3 as a potent Th2 inducer in a human skin system, paving the way towards accurate modeling of the initiation steps of atopic dermatitis.

Vitamin D3 promotes human Th2 responses by TSLP-dependent and -independent regulation of dendritic cells