Distinct fibroblast subsets drive inflammation and damage in arthritis

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Distinct fibroblast subsets drive inflammation and damage in arthritis. / Croft, Adam P.; Campos, Joana; Jansen, Kathrin; Turner, Jason D.; Marshall, Jennifer; Attar, Moustafa; Savary, Loriane; Wehmeyer, Corinna; Naylor, Amy J.; Kemble, Samuel; Begum, Jenefa; Dürholz, Kerstin; Perlman, Harris; Barone, Francesca; Mcgettrick, Helen M.; Fearon, Douglas T.; Wei, Kevin; Raychaudhuri, Soumya; Korsunsky, Ilya; Brenner, Michael B.; Coles, Mark; Sansom, Stephen N.; Filer, Andrew; Buckley, Christopher D.

In: Nature, Vol. 570, No. 7760, 29.05.2019, p. 246–251 .

Research output: Contribution to journalArticle

Harvard

Croft, AP, Campos, J, Jansen, K, Turner, JD, Marshall, J, Attar, M, Savary, L, Wehmeyer, C, Naylor, AJ, Kemble, S, Begum, J, Dürholz, K, Perlman, H, Barone, F, Mcgettrick, HM, Fearon, DT, Wei, K, Raychaudhuri, S, Korsunsky, I, Brenner, MB, Coles, M, Sansom, SN, Filer, A & Buckley, CD 2019, 'Distinct fibroblast subsets drive inflammation and damage in arthritis', Nature, vol. 570, no. 7760, pp. 246–251 . https://doi.org/10.1038/s41586-019-1263-7

APA

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Author

Croft, Adam P. ; Campos, Joana ; Jansen, Kathrin ; Turner, Jason D. ; Marshall, Jennifer ; Attar, Moustafa ; Savary, Loriane ; Wehmeyer, Corinna ; Naylor, Amy J. ; Kemble, Samuel ; Begum, Jenefa ; Dürholz, Kerstin ; Perlman, Harris ; Barone, Francesca ; Mcgettrick, Helen M. ; Fearon, Douglas T. ; Wei, Kevin ; Raychaudhuri, Soumya ; Korsunsky, Ilya ; Brenner, Michael B. ; Coles, Mark ; Sansom, Stephen N. ; Filer, Andrew ; Buckley, Christopher D. / Distinct fibroblast subsets drive inflammation and damage in arthritis. In: Nature. 2019 ; Vol. 570, No. 7760. pp. 246–251 .

Bibtex

@article{89d44c42334a49c4a8b941fb6dfd7c94,
title = "Distinct fibroblast subsets drive inflammation and damage in arthritis",
abstract = "The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs). However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1− destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1− fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.",
author = "Croft, {Adam P.} and Joana Campos and Kathrin Jansen and Turner, {Jason D.} and Jennifer Marshall and Moustafa Attar and Loriane Savary and Corinna Wehmeyer and Naylor, {Amy J.} and Samuel Kemble and Jenefa Begum and Kerstin D{\"u}rholz and Harris Perlman and Francesca Barone and Mcgettrick, {Helen M.} and Fearon, {Douglas T.} and Kevin Wei and Soumya Raychaudhuri and Ilya Korsunsky and Brenner, {Michael B.} and Mark Coles and Sansom, {Stephen N.} and Andrew Filer and Buckley, {Christopher D.}",
year = "2019",
month = "5",
day = "29",
doi = "10.1038/s41586-019-1263-7",
language = "English",
volume = "570",
pages = "246–251",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7760",

}

RIS

TY - JOUR

T1 - Distinct fibroblast subsets drive inflammation and damage in arthritis

AU - Croft, Adam P.

AU - Campos, Joana

AU - Jansen, Kathrin

AU - Turner, Jason D.

AU - Marshall, Jennifer

AU - Attar, Moustafa

AU - Savary, Loriane

AU - Wehmeyer, Corinna

AU - Naylor, Amy J.

AU - Kemble, Samuel

AU - Begum, Jenefa

AU - Dürholz, Kerstin

AU - Perlman, Harris

AU - Barone, Francesca

AU - Mcgettrick, Helen M.

AU - Fearon, Douglas T.

AU - Wei, Kevin

AU - Raychaudhuri, Soumya

AU - Korsunsky, Ilya

AU - Brenner, Michael B.

AU - Coles, Mark

AU - Sansom, Stephen N.

AU - Filer, Andrew

AU - Buckley, Christopher D.

PY - 2019/5/29

Y1 - 2019/5/29

N2 - The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs). However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1− destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1− fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.

AB - The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune-mediated inflammatory diseases (IMIDs). However, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue-driven processes observed in IMIDs, such as inflammation and damage. Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of fibroblast activation protein-α (FAPα)+ fibroblasts suppressed both inflammation and bone erosions in mouse models of resolving and persistent arthritis. Single-cell transcriptional analysis identified two distinct fibroblast subsets within the FAPα+ population: FAPα+THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPα+THY1− destructive fibroblasts restricted to the synovial lining layer. When adoptively transferred into the joint, FAPα+THY1− fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation, whereas transfer of FAPα+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell-based therapies aimed at modulating inflammation and tissue damage.

UR - http://www.scopus.com/inward/record.url?scp=85066788177&partnerID=8YFLogxK

U2 - 10.1038/s41586-019-1263-7

DO - 10.1038/s41586-019-1263-7

M3 - Article

VL - 570

SP - 246

EP - 251

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7760

ER -