Keratinocyte-derived TGFβ is not required to maintain skin immune homeostasis

Transforming growth factor beta 1 (TGFβ) is known to be a regulator of autoimmunity. Loss of TGFβ leads to severe multi-organ autoimmunity in mice. In skin, role of TGFβ in suppressing autoimmunity is unclear.

Determine whether Keratinocyte (KC)-derived TGFβ is required for skin immune homeostasis.

We generated K14-CreER^T2TGFβ1^fl/fl (TGFβ^ΔKC) mice allowing for tamoxifen-induced deletion of TGFβ1 in KC. The phenotype of skin was analyzed and compared to mice in which epidermal activation of TGFβ is impaired.

KC was the major source of TGFβ in epidermis. Topical tamoxifen application led to efficient TGFβ1 deletion. The expected acanthosis was observed but no inflammatory infiltrate or altered numbers of resident immune cells were evident. Similarly, Itgb6^-/-x K14Cre Itgb8^f/f (Itgb6^-/-Itgb8^ΔKC) mice lacking both epidermal TGFβ-activating integrins showed no evidence of cutaneous inflammation.

KC-derived TGFβ and epidermal TGFβ activation are not required to suppress skin autoimmunity in steady state.