# TAZ deficiency exacerbates psoriatic pathogenesis by increasing the histamine-releasing factor

## TL;DR

TAZ deficiency worsens psoriasis by increasing histamine-releasing factor (HRF) levels in immune cells, leading to more severe inflammation.

## Contribution

This study reveals a novel role of TAZ in controlling HRF protein stability and psoriasis progression.

## Key findings

- TAZ deficiency increases HRF expression and secretion in mast cells.
- TAZ deficiency leads to more severe imiquimod-induced psoriasis in mice.
- TAZ regulates HRF protein stability, not transcription.

## Abstract

Transcriptional coactivator with PDZ-biding motif (TAZ) is widely expressed in most tissues and interacts with several transcription factors to regulate cell proliferation, differentiation, and death, thereby influencing organ development and size control. However, very little is known about the function of TAZ in the immune system and its association with inflammatory skin diseases, so we investigated the role of TAZ in the pathogenesis of psoriasis.

Interestingly, TAZ was expressed in mast cells associated, particularly in lysosomes, and co-localized with histamine-releasing factor (HRF). TAZ deficiency promoted mast cell maturation and increased HRF expression and secretion by mast cells. The upregulation of HRF in TAZ deficiency was not due to increased transcription but to protein stabilization, and TAZ restoration into TAZ-deficient cells reduced HRF protein. Interestingly, imiquimod (IMQ)-induced psoriasis, in which HRF serves as a major pro-inflammatory factor, was more severe in TAZ KO mice than in WT control. HRF expression and secretion were increased by IMQ treatment and were more pronounced in TAZ KO mice treated with IMQ.

Thus, as HRF expression was stabilized in TAZ KO mice, psoriatic pathogenesis progressed more rapidly, indicating that TAZ plays an important role in preventing psoriasis by regulating HRF protein stability.

HRF is expressed in lysosomes and associated with TAZ expression.HRF expression is increased in TAZ-deficient immune cells.HRF protein stability is controlled by TAZ, resulting in stabilized HRF in TAZ deficiency.TAZ deficiency promotes susceptibility to IMQ-induced psoriasis, leading to exacerbated psoriatic inflammation.

HRF is expressed in lysosomes and associated with TAZ expression.

HRF expression is increased in TAZ-deficient immune cells.

HRF protein stability is controlled by TAZ, resulting in stabilized HRF in TAZ deficiency.

TAZ deficiency promotes susceptibility to IMQ-induced psoriasis, leading to exacerbated psoriatic inflammation.