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

• Published in: Journal of dermatological science 2019-05, Vol.94 (2), p.290-297
• Main Authors: Yang, Yi, Zenke, Yukari, Hirai, Toshiro, Kaplan, Daniel H.
• Format: Article
• Language: English
• Subjects: Animals; Autoimmunity; Gene Knockout Techniques; Keratinocyte; Keratinocytes - immunology; Keratinocytes - metabolism; Mice; Mice, Knockout; Models, Animal; Skin; Skin - cytology; Skin - immunology; Skin - metabolism; Tamoxifen - pharmacology; TGFβ; Transforming Growth Factor beta1 - genetics; Transforming Growth Factor beta1 - immunology; Transforming Growth Factor beta1 - metabolism; αvβ6; αvβ8
• ISSN: 0923-1811; 1873-569X
• DOI: 10.1016/j.jdermsci.2019.04.008

•K14-CreERT2TGFβ1fl/fl mice develop acanthosis.•K14-CreERT2TGFβ1fl/fl mice do not develop spontaneous skin inflammation.•Itgb6−/−x K14Cre Itgb8f/f mice do not develop spontaneous skin inflammation. 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-CreERT2TGFβ1fl/fl (TGFβΔKC) 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 Itgb8f/f (Itgb6−/−Itgb8ΔKC) 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.