Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) in keratinocyte and cytokine signalling drives human Th17 response in psoriasis

Transcriptional factor B lymphocyte-induced maturation protein 1 (Blimp-1) is pivotally implicated in T helper 17 (Th17) cell differentiation. This study investigated expression of the Blimp-1 protein, positive regulatory domain 1 ( PRDM1 ), and cytokine genes in psoriasis (PsO). Affected (AS-PsO) and non-affected skin (nAS-PsO) samples were used to assess gene and protein expressions by reverse transcription-quantitative PCR (RT-qPCR), and immunostaining and confocal microscopy, respectively; the normalised public transcriptomic data permitted differential gene expression analyses. On RT-qPCR, PRDM1 and IL17A transcripts showed higher expression in AS-PsO than in nAS-PsO ( n = 34) ( p < 0.001; p < 0.0001, respectively). Confocal microscopy showed Blimp-1 protein expression in epidermal layer keratinocytes in AS-PsO, but not in nAS-PsO. Bioinformatic analysis of the transcriptomic dataset GSE13355 corroborated the increased PRDM1 , signal transducer and activator of transcription 3 ( STAT3 ), IL12B , TNF , IL17A , IL6 , IL1B , IL22 , and IL10 gene expression in AS-PsO, when compared to normal skin and nAS-PsO ( p < 0.001). PRDM1 expression correlated positively ( p < 0.0001) with that of IL17A ( r = 0.7), IL1B ( r = 0.67), IL12B ( r = 0.6), IL6 ( r = 0.59), IL22 ( r = 0.53), IL23A ( r = 0.47), IL21 ( r = 0.47), IL27 ( r = 0.34), IL23R ( r = 0.32), S100 calcium binding protein A9 ( r = 0.63), and lipocalin 2 ( r = 0.50), and negatively with that of TGFB1 ( r = − 0.28) and RORC ( r = − 0.60). Blimp-1 may be critical in the pathogenesis of PsO dysregulation involving the Th17 inflammatory pathway. This knowledge may accelerate the development of new treatments.