Auf1/Hnrnpd-deficient mice develop pruritic inflammatory skin disease.

Mice lacking heterogenous nuclear ribonuclear protein D (Hnrnpd), also known as Auf1, a regulator of inflammatory cytokine mRNA stability, develop chronic dermatitis with age that is characterized by pruritus and excoriations. Histological analysis showed marked epidermal acanthosis and spongiosis, neovascularization, and elevated number of inflammatory cells, including T cells, macrophages, neutrophils, mast cells, and eosinophils. Hnrnpd-deficient (Hnrnpd(tm1Rjsc)) mice with dermatitis display elevated serum IgE levels. Lesions in Hnrnpd(tm1Rjsc) mice were associated with a shift towards a Th(2) immune environment. Evaluation of T-cell-mediated skin inflammation by assaying contact hypersensitivity indicated an increased response in Hnrnpd(tm1Rjsc) mice. T cells and macrophages from Hnrnpd(tm1Rjsc) mice demonstrate a number of abnormalities associated with dermatitis, including increased IL2, tumor-necrosis factor-alpha (TNFalpha), and IL1beta production. Finally, many features of spontaneous dermatitis could be recapitulated in experimentally induced lesions by subcutaneous injection of CCL27 and TNF in unaffected Hnrnpd(tm1Rjsc) mice. Collectively, these data highlight the importance of HNRNPD and proper regulation of mRNA stability in the intricate processes of leukocyte recruitment and inflammatory activation within the skin.