RESUMO
In the skin, Langerhans cells (LCs) require autocrine latent TGFß that is transactivated by the integrins ανß6 and ανß8 expressed by keratinocytes (KCs) for long-term epidermal retention. Selective expression of a ligand-independent, constitutively active form of TGFßR1 inhibits LC migration during homeostasis and in response to UVB exposure. In this study, we found that LC migration in response to inflammatory stimuli was also inhibited by ligand-independent TGFßR1 signaling. Contrary to UVB stimulation, which reduced KC expression of ανß6, in vitro and in vivo exposure to TNF-α or IL-1ß increased ανß6 transcript and protein expression by KCs. This resulted in increased KC-mediated transactivation of latent TGFß. Expression of ανß8 was largely unchanged. These findings show that ligand-independent TGFßR1 signaling in LCs can overcome inflammatory migration stimuli, but reduced KC-mediated transactivation of latent TGFß by KCs may only drive LC migration during homeostasis and in response to UV stimulation.
