TY - JOUR
T1 - Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa
AU - van Straalen, Kelsey R.
AU - Ma, Feiyang
AU - Tsou, Pei Suen
AU - Plazyo, Olesya
AU - Gharaee-Kermani, Mehrnaz
AU - Calbet, Marta
AU - Xing, Xianying
AU - Sarkar, Mrinal K.
AU - Uppala, Ranjitha
AU - Harms, Paul W.
AU - Wasikowski, Rachael
AU - Nahlawi, Lina
AU - Nakamura, Mio
AU - Eshaq, Milad
AU - Wang, Cong
AU - Dobry, Craig
AU - Kozlow, Jeffrey H.
AU - Cherry-Bukowiec, Jill
AU - Brodie, William D.
AU - Wolk, Kerstin
AU - Uluçkan, Özge
AU - Mattichak, Megan N.
AU - Pellegrini, Matteo
AU - Modlin, Robert L.
AU - Maverakis, Emanual
AU - Sabat, Robert
AU - Kahlenberg, J. Michelle
AU - Billi, Allison C.
AU - Tsoi, Lam C.
AU - Gudjonsson, Johann E.
N1 - Publisher Copyright: © 2023, van Straalen et al.
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.
AB - Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.
UR - https://www.scopus.com/pages/publications/85184143895
U2 - 10.1172/JCI169225
DO - 10.1172/JCI169225
M3 - Article
C2 - 38051587
AN - SCOPUS:85184143895
SN - 0021-9738
VL - 134
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 3
M1 - e169225
ER -