Langerhans cells rely on good neighbors to overcome gene deficiencies.

Abstract

Abstract We recently identified that epidermal resident Langerhans Cells (LCs) acquire gene expression fingerprints from surrounding Keratinocytes (KCs) in the form of mRNA and protein. In the present study, we aimed to determine whether this transfer can also overcome gene deficiencies. For this purpose, using the Cre/Lox system, we specifically deleted genes for Connexin 43 (Cx43), MyD88, and MHC-II in LCs. While all three genes underwent recombination, reduced protein levels were only observed for MHC-II, whereas Cx43 and MyD88 protein levels remained unaltered. Considering that KCs lack MHC-II, but express Cx43 and MyD88 at high levels, we posit that LCs can acquire gene products from surrounding KCs to overcome their own deficiencies if those products are available. In summary, we present evidence that cells can compensate for gene deficiencies if the surrounding cells can provide. These findings highlight the limitations of cell-specific gene deletion, and could provide an explanation as to why certain gene deletions do not lead to measurable deficiencies.