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.
Sadri
Navid
N
Department of Microbiology, New York University School of Medicine, New York, New York 10003, USA.
Schneider
Robert J
RJ
D000818:Animals; D054425:Chemokine CCL27 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003872:Dermatitis / Q000378:metabolism; D005260:Female; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics* / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D011537:Pruritus / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C492276:CCL27 protein, human; D054425:Chemokine CCL27; D016207:Cytokines; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D053583:Interleukin-1beta; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases