982 Keratinocytes derived TGFβ is not required for immune homeostasis in mouse skin

Abstract

TGFβ is essential the epidermal retention resident memory T cells and Langerhans cells, but the source of TGFβ that is important for these functions is unknown. Since the majority of cells in epidermis are keratinocytes (KC), we hypothesized that TGFβ from KC might be important for skin homeostasis and the maintenance of skin immune cells. To examine this, we generated K14CreERT2TGFβflYFP mice which enables tamoxifen inducible specifically ablation of TGFβ in KC. Systemic application of tamoxifen was lethal likely due to esophageal inflammation. Topical application of 4-hydroxytamoxifen (4-OHT) once a day for 2 days was well tolerated. We confirmed the deletion of TGFβ in bulge, isthumus and interfollicular keratinocytes based on YFP expression and TGFβ mRNA 28 and 84 days post 4-OHT treatment. Mice with KC specific deletion of TGFβ developed acanthosis without observable skin inflammation, implicating a TGFβ autocrine/paracrine suppression of KC proliferation. We also found that ablation of TGFβ in KC has no effect on the numbers of epidermal-resident Langerhans cell, αβ T cells and Innate lymphoid. A modest decrease in DETC was observed. In dermis, we did not find any alteration in numbers of DC subsets, αβ T cells or dermal γδ T cells. Thus, under homeostatic conditions deletion of TGFβ in KC enhances epidermal acanthosis but has limited effect on cutaneous residence of most immune cells.