TY - JOUR
T1 - Human Mast Cells Upregulate Cathepsin B, a Novel Marker of Itch in Psoriasis
AU - West, Peter W
AU - Tontini, Chiara
AU - Atmoko, Haris
AU - Kiss, Orsolya
AU - Garner, Terence
AU - Bahri, Rajia
AU - Warren, Richard B
AU - Griffiths, Christopher E M
AU - Stevens, Adam
AU - Bulfone-Paus, Silvia
N1 - Funding Information:
H.A. was supported by a PhD studentship from the Psoriasis Association.
Funding Information:
The authors declare no conflict of interest. C.T. and R.B. were supported by funding from the Medical Research Council (UK). R.B.W. is supported by the Manchester NIHR Biomedical Research Centre.
Funding Information:
The Bioimaging Facility microscopes used in this study were purchased with grants from BBSRC, Wellcome, and the University of Manchester Strategic Fund. Special thanks goes to the bioimaging staff for their help with microscopy. The Flow Cytometry Facility equipment used in this study was supported by funding from the Manchester Collaborative Centre for Inflammation Research, Wellcome Trust, and University of Manchester Strategic Fund. The authors thank Gareth Howell for technical support with cell sorting.
Publisher Copyright:
© 2023 by the authors.
PY - 2023/8/30
Y1 - 2023/8/30
N2 - Mast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibres and disease severity, and molecular signature by comparing RNA-seq analysis of MCs isolated from the skin of psoriasis patients and healthy volunteers. In involved psoriasis skin, MCs and Calcitonin Gene-Related Peptide (CGRP)-positive nerve fibres were spatially associated, and the increase of both MC and nerve fibre density correlated with disease severity. Gene set enrichment analysis of differentially expressed genes in involved psoriasis skin showed significant representation of neuron-related pathways (i.e., regulation of neuron projection along with dendrite and dendritic spine morphogenesis), indicating MC engagement in neuronal development and supporting the evidence of close MC-nerve fibre interaction. Furthermore, the analysis of 208 identified itch-associated genes revealed that
CTSB,
TLR4, and
TACR1 were upregulated in MCs in involved skin. In both whole-skin published datasets and isolated MCs,
CTSB was found to be a reliable indicator of the psoriasis condition. Furthermore, cathepsin B+ cells were increased in psoriasis skin and cathepsin B+ MC density correlated with disease severity. Therefore, our study provides evidence that cathepsin B could serve as a common indicator of the MC-dependent itch signature in psoriasis.
AB - Mast cells (MCs) contribute to skin inflammation. In psoriasis, the activation of cutaneous neuroimmune networks commonly leads to itch. To dissect the unique contribution of MCs to the cutaneous neuroinflammatory response in psoriasis, we examined their density, distribution, relation to nerve fibres and disease severity, and molecular signature by comparing RNA-seq analysis of MCs isolated from the skin of psoriasis patients and healthy volunteers. In involved psoriasis skin, MCs and Calcitonin Gene-Related Peptide (CGRP)-positive nerve fibres were spatially associated, and the increase of both MC and nerve fibre density correlated with disease severity. Gene set enrichment analysis of differentially expressed genes in involved psoriasis skin showed significant representation of neuron-related pathways (i.e., regulation of neuron projection along with dendrite and dendritic spine morphogenesis), indicating MC engagement in neuronal development and supporting the evidence of close MC-nerve fibre interaction. Furthermore, the analysis of 208 identified itch-associated genes revealed that
CTSB,
TLR4, and
TACR1 were upregulated in MCs in involved skin. In both whole-skin published datasets and isolated MCs,
CTSB was found to be a reliable indicator of the psoriasis condition. Furthermore, cathepsin B+ cells were increased in psoriasis skin and cathepsin B+ MC density correlated with disease severity. Therefore, our study provides evidence that cathepsin B could serve as a common indicator of the MC-dependent itch signature in psoriasis.
KW - cathepsin B
KW - itch
KW - mast cells
KW - psoriasis
U2 - 10.3390/cells12172177
DO - 10.3390/cells12172177
M3 - Article
C2 - 37681909
SN - 2073-4409
VL - 12
JO - Cells
JF - Cells
IS - 17
M1 - 2177
ER -