| First Author | Bobr A | Year | 2012 |
| Journal | Proc Natl Acad Sci U S A | Volume | 109 |
| Issue | 26 | Pages | 10492-7 |
| PubMed ID | 22689996 | Mgi Jnum | J:185586 |
| Mgi Id | MGI:5429454 | Doi | 10.1073/pnas.1119178109 |
| Citation | Bobr A, et al. (2012) Autocrine/paracrine TGF-beta1 inhibits Langerhans cell migration. Proc Natl Acad Sci U S A 109(26):10492-7 |
| abstractText | Langerhans cells (LCs) are skin-resident dendritic cells (DC) located in the epidermis that migrate to skin-draining lymph nodes during the steady state and in response to inflammatory stimuli. TGF-beta1 is a critical immune regulator that is highly expressed by LCs. The ability to test the functional importance of LC-derived TGF-beta1 is complicated by the requirement of TGF-beta1 for LC development and by the absence of LCs in mice with an LC-specific ablation of TGF-beta1 or its receptor. To overcome these problems, we have engineered transgenic huLangerin-CreER(T2) mice that allow for inducible LC-specific excision. Highly efficient and LC-specific expression was confirmed in mice bred onto a YFP Cre reporter strain. We next generated huLangerin-CreER(T2) x TGF-betaRII(fl) and huLangerin-CreER(T2) x TGF-beta1(fl) mice. Excision of the TGFbetaRII or TGFbeta1 genes induced mass migration of LCs to the regional lymph node. Expression of costimulatory markers and inflammatory cytokines was unaffected, consistent with homeostatic migration. In addition, levels of p-SMAD2/3 were decreased in LCs from wild-type mice before inflammation-induced migration. We conclude that TGF-beta1 acts directly on LCs in an autocrine/paracrine manner to inhibit steady-state and inflammation-induced migration. This is a readily targetable pathway with potential therapeutic implications for skin disease. |
