929 TH2 and TH17 cell differentiation is differentially regulated by innate anti-viral protein Trim32

Abstract

Pellagra, acrodermatitis enteropathica and biotin deficiency are caused by the deficiency of specific nutrients. These patients commonly present with similar skin dermatosis and show shared histological alterations, including vacuolization and necrosis of keratinocytes in epidermis. Recent studies have shown that number of epidermal Langerhans cells decreased at these skin lesions. However, the precise reasons, why Langerhans cells decrease or disappeared, have not yet been elucidated. In this study, we generated several nutrition deficient model mice including pellagra. After BALB/c mice were fed with niacin-deficient diet or control diet for 4 to 12 weeks (n¼3-6), we performed microarray analysis using RNA extracted from mice skin. We found Langerhans cells determined by CD207 were substantially decreased or eventually disappeared in pellagra model mice skin even without any pathological change. The microarray data also shows the decreased expression of CD209 (DC-SIGN), which expressed in dermal and mucous tissue, lymphoid tissue, as well as on monocyte-derived dendritic cells. In addition, the expressions of CCR2, CCL7 and CCL8 were also significantly downregulated in pellagra mice. In the inflamed skin, the activation of CCR2 by CCL2 or CCL7 is known to be essential for the recruitment of blood-borne precursor cells of Langerhans cells. Our observations suggest that the lack of niacin disturbs the crucial expression of CCL7, CCL8 and the subsequent absence of Langerhans cells is caused by the loss of recruitment of precursor cells to the lesional skin after prolonged inflammation.