This ability of keratinocytes has been shown to be dysregulated in AE lesional skin. It is known that BAFF and APRIL can be expressed by resident cells in several kinds of tissues. We report here that healthy keratinocytes can also synthesize and express BAFF and APRIL, both in vivo and ex vivo, and in lesional skin of AE, APT-AE and SE the keratinocytes have impaired APRIL expression compared to HCs. Different from other TNF ligands, APRIL only functions as a soluble protein. By immunohistological analysis, we confirmed the intracellular expression pattern of APRIL in keratinocytes both in vivo and ex vivo, which is different from the cell membrane associated expression pattern of BAFF. We then studied the regulation of BAFF and APRIL in vitro in keratinocytes using some factors involved in the pathogenesis of eczema and we found that the BAFF mRNA level was dramatically increased by IFN-c and IL-27. IL-27 is a member of the IL-12 family, produced by activated APCs. The increased expression of IFN-c and IL-27 in chronic eczema skin lesions has been demonstrated before, and both IFN-c and IL-27 have been shown to greatly induce the production of CXCL 9�?1 in normal human keratinocytes, the chemokines known to attract Th1 cells, triggering and Y-27632 dihydrochloride sustaining skin inflammation. Here we suggest that IFN-c and IL-27 can amplify the skin inflammation not only through the regulation of the chemokine production in keratinocytes, but also through the regulation of BAFF expression in these cells. By immunostaining we did not found the expression of TACI or BAFFR by keratinocytes both in vivo and ex vivo, indicating that the expression of BAFF and APRIL by keratinocytes is not regulated by feedback autocrine mechanism. BAFF and APRIL thus presumably have no regulatory role for the homeostasis of keratinocytes. TACI and BAFFR are mainly expressed by B-cells and the presence of B-cells in normal skin and the infiltration of B-cells in AE eczema skin have been demonstrated by Simon et al. We could detect the expression of these two receptors in skin, however, the mRNA level of these two receptors in inflamed skin of APT-AE, AE and SE was not found to be increased. The reason for this could be the dilute effect by the influx of a large number of T-cells and macrophages in inflammatory skin lesions. Indeed, when the mRNA levels of these two receptors were normalized to the expression level of a B-cells maker CD19, the relative mRNA expression of TACI and BAFFR appeared similar in all groups. APRIL is a close homologue to BAFF and they share many functions and receptors. Here we demonstrate that opposite to BAFF, the expression of APRIL, as well as the cell surface APRIL hybrid TWE-PRIL, is down-regulated in the skin lesions of APTAE, AE and SE. It has been shown that APRIL binding to TACI delivers a negative signal to B-cells.