MIP3 alpha stimulates the migration of Langerhans cells in models of human papillomavirus (HPV)-associated (pre)neoplastic epithelium

Although human papillomavirus (HPV) DNA is detected in the majority of cervical cancers and their precursors (squamous intraepithelial lesions; SIL), the persistence or progression of cervical lesions could be associated with quantitative and functional alterations of dendritic/Langerhans cells (DC/LC). As LC abnormalities have been associated with a decreased expression of macrophage inflammatory protein 3α (MIP3α) in cervical SIL, we tested the effect of exogenous MIP3α on the migration of LC in a (pre)neoplastic epithelium formed in vitro. By using a Boyden chamber assay, we first showed that the migratory capacity of LC generated in vitro is significantly increased in the presence of MIP3α compared to control medium. We next demonstrated that MIP3α is able to increase the 3D infiltration of LC in organotypic cultures of HPV-transformed keratinocytes. This property to stimulate LC migration was not altered after inclusion of MIP3α in a bioadhesive polycarbophil gel. Moreover, the function of DC to exert cytostatic effects and to present alloantigens was not altered in the presence of MIP3α. P. Hubert and L. Herman contributed equally to this work.