B lymphocyte-induced maturation protein 1 (BLIMP1) is a transcriptional repressor that controls the differentiation and function of many immune cell populations. This study describes an anti-inflammatory role for BLIMP1 in the adult epidermis. Mice specifically lacking BLIMP1 in keratinocytes spontaneously developed skin inflammation, which was characterized by alopecia, ulceration and inflammatory cell infiltrates. Keratinocytes lacking BLIMP1 showed increased expression of pro-inflammatory cytokines and chemokines, including interleukin-1α, CXC-chemokine ligand 1 and granulocyte colony-stimulating factor (G-CSF). Further analyses suggested that BLIMP1 does not directly repress these pro-inflammatory factors, but instead regulates their expression indirectly by repressing the AP-1 family members Fos and Fosl1. Notably, the authors found that BLIMP1 is expressed in healthy human skin, but its expression is reduced in the skin of patients with eczema.