A role for TGFβ1 in Langerhans cell biology: Further characterization of the epidermal Langerhans cell defect in TGFβ1 null mice

Previous studies of TGFβ1 null (-/-) mice indicated that the epidermis was devoid of Langerhans cells (LC) and that the LC deficiency was not secondary to the inflammation that is the dominant feature of the -/- phenotype (Borkowski, T.A., J.J. Letterio, A.G. Farr, and M.C. Udey. 1996. J. Exp. Med. 184:2417-2422). Herein, we demonstrate that dendritic cells could be expanded from the bone marrow of -/- mice and littermate controls. Bone marrow from -/- mice also gave rise to LC after transfer into lethally irradiated recipients. Thus, the LC defect in TGFβ1 null mice does not result from an absolute deficiency in bone marrow precursors, and paracrine TGFβ1 production is sufficient for LC development. Several approaches were used to assess the suitability of -/- skin for LC localization. A survey revealed that although a number of cytokine mRNAs were expressed de novo, mRNAs encoding proinflammatory cytokines known to mobilize LC from epidermis (IL-1 and TNFα) were not strikingly overrepresented in -/- skin. In addition, bone marrow-derived LC populated full-thickness TGFβ1 null skin after engraftment onto BALB/c nu/nu recipients. Finally, the skin of transgenic mice expressing a truncated loricrin promoter-driven dominant- negative TGFβ type II receptor contained normal numbers of LC. Because TGFβ1 signaling in these mice is disrupted only in keratinocytes and the keratinocyte hyperproliferative component of the TGFβ1 -/- phenotype is reproduced, these results strongly suggest that the LC defect in TGFβ1 null mice is not due to an epidermal abnormality but reflects a requirement of murine LC (or their precursors) for TGFβ1.