Frontal fibrosing alopecia shows robust T helper 1 and Janus kinase 3 skewing

Abstract

Summary Background Frontal fibrosing alopecia (FFA) is a scarring alopecia with unclear pathogenesis and a progressive course. The disease has a major impact on patients’ quality of life and there is a lack of effective treatment to halt disease progression. Methods We profiled lesional and nonlesional scalp biopsies collected in 2017 from patients with FFA (n = 12) compared with scalp biopsies from patients with alopecia areata (AA) (n = 8) and controls (n = 8) to evaluate gene and protein expression, including the primary outcome (CXCL9). We determined significant differences between biomarkers using a two‐sided Student's t‐test adjusting P‐values by false discovery rate. Results Significant increases were seen in CD8+ cytotoxic T cells, CD11c+ dendritic cells, CD103+ and CD69+ tissue‐resident memory T cells in FFA and AA vs. control scalp (P < 0·05), with corresponding significantly upregulated granzyme B mRNA, particularly in FFA (P < 0·01). In AA, cellular infiltrates were primarily concentrated at the bulb, while in FFA these were mainly localized at the bulge. FFA demonstrated significant upregulation of T helper 1/intereferon (IFN) (IFN‐γ, CXCL9/CXCL10), the Janus kinase/signal transducers and activators of transcription (JAK‐STAT) pathway (STAT1, JAK3) and fibrosis‐related products (vimentin, fibronectin; P < 0·05), with no concomitant downregulation of hair keratins and the T‐regulatory marker, forkhead box P3, which were decreased in AA. The stem cell markers CD200 and K15 demonstrated significantly reduced expression only in FFA (P < 0·05). Conclusions These data suggest that follicular damage and loss of stem cells in FFA may be mediated through immune attack in the bulge region, with secondary fibrosis and reduced but still detectable stem cells. JAK/STAT‐targeting treatments may be able to prevent permanent follicular destruction and fibrosis in early disease stages.

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

“…Further reinforcing the concept of immune dysregulation in driving fibrotic processes in keloids is the increased T-cell expression, including Th2-related markers, in several fibrotic conditions, such as frontal fibrosing alopecia and scleroderma (65,66). In vitro studies have also demonstrated the profibrotic effects of the type 2 cytokines IL-4 and IL-13 (22), including increased collagen production in keloid fibroblasts after IL-13 stimulation (67).…”

Frontal Fibrosing Alopecia: A Review

“…Regarding the composition of the inflammatory infiltrate in FFA, this is characterized by an increase in the percentage of CD8+ T cells [ 37 , 172 ], with a reversal of the typical CD4:CD8 ratio (which is approximately 2:1). However, this ratio is increased (>3:1) in uninvolved follicles in FFA, which may be because of the migration of CD8+ T cells from uninvolved areas to involved ones [ 170 ].…”

Resident Memory T Cells in Autoimmune Skin Diseases

“…Del Duca et al. recently determined that lesional skin from AA and FFA patients has significantly more CD8+ cytotoxic T cells, CD11c+ dendritic cells, and CD103+ CD69+ TRM cells when compared to nonlesional skin ( 87 ). In particular, FFA was shown to have a significant upregulation of the IFNγ/CXCL9/CXCL10 pathway and the JAK-STAT pathway ( 88 ), ( Figure 2D ).…”