Hapten application to skin recruits monocyte-derived LC precursors to epidermis. Flow cytometry analysis of epidermis 7 days after 2,4,6-trinitro-1-chlorobenzene application in WT or CD11c-p14del mice reveals the recruitment of CD45⁺MHC II⁺ cells into epidermis. In CD11c-p14del epidermis, although a subset of recruited cells acquires langerin expression to become short-term LCs, the major fraction remains langerin-negative suggesting that monocyte-to-LC differentiation is arrested at the pre-LC stage. Thus, together with the authors’ in situ and in vitro data, in the absence of p14, short-term LCs appear not to proliferate and rather, undergo apoptosis, failing to establish LC networks. Long-term LCs also fail to prevail. See Figure 6A in the article by Sparber et al that begins on page 217.