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Type 2 lymphocytes restrict type 3 lymphocytes during liver fibrosis and colocalize in fibroblast niches

Sbierski-Kind, Julia ; Cautivo, Kelly M. ; Nilsson, Julia LU ; Wagner, Johanna C. ; Dahlgren, Madelene W. LU orcid ; Crystal, Nathan Ewing ; McClave, Maria ; Mroz, Nicholas M. ; Ganslmeier, Marlene and Lizama, Carlos O. , et al. (2026) In Science Advances 12(11). p.1-21
Abstract

Fibroblasts are dynamic structural cells that direct both beneficial tissue repair and pathological organ fibrosis through interactions with tissue-resident type 2 lymphocytes (T2Ls) and type 3/17 lymphocytes (T3Ls). The cytokines interleukin-13 (IL-13) and IL-17A, produced by T2Ls and T3Ls, respectively, are linked to both tissue inflammation and fibrosis, but how their spatial positioning influences beneficial or pathological organ remodeling remains unclear. Using mouse models of liver injury and fibrosis, three-dimensional microscopy, and spatial transcriptomics, we found an accumulation of periportal and fibrotic tract T2Ls, predominantly group 2 innate lymphoid cells (ILC2s), positioned near T3Ls and niche adventitial fibroblasts... (More)

Fibroblasts are dynamic structural cells that direct both beneficial tissue repair and pathological organ fibrosis through interactions with tissue-resident type 2 lymphocytes (T2Ls) and type 3/17 lymphocytes (T3Ls). The cytokines interleukin-13 (IL-13) and IL-17A, produced by T2Ls and T3Ls, respectively, are linked to both tissue inflammation and fibrosis, but how their spatial positioning influences beneficial or pathological organ remodeling remains unclear. Using mouse models of liver injury and fibrosis, three-dimensional microscopy, and spatial transcriptomics, we found an accumulation of periportal and fibrotic tract T2Ls, predominantly group 2 innate lymphoid cells (ILC2s), positioned near T3Ls and niche adventitial fibroblasts and adjacent to discrete profibrotic myofibroblasts. Unexpectedly, T2L ablation worsened both carbon tetrachloride– and bile duct ligation–induced liver fibrosis, accompanied by increased IL-17A+ T3Ls, predominantly γδ T cells. In contrast, concurrent T2L and T3L ablation reduced liver fibrosis. Our work suggests a spatially associated cross-talk between liver lymphocytes and fibroblast niches that tunes liver repair but can go awry in pathological liver fibrosis.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Science Advances
volume
12
issue
11
article number
eaea6805
pages
21 pages
publisher
American Association for the Advancement of Science (AAAS)
external identifiers
  • pmid:41811951
  • scopus:105033309844
ISSN
2375-2548
DOI
10.1126/sciadv.aea6805
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2026 The Authors
id
4974d38a-3878-45f1-823b-af2cb369a3d1
date added to LUP
2026-04-23 13:48:01
date last changed
2026-05-21 15:37:43
@article{4974d38a-3878-45f1-823b-af2cb369a3d1,
  abstract     = {{<p>Fibroblasts are dynamic structural cells that direct both beneficial tissue repair and pathological organ fibrosis through interactions with tissue-resident type 2 lymphocytes (T2Ls) and type 3/17 lymphocytes (T3Ls). The cytokines interleukin-13 (IL-13) and IL-17A, produced by T2Ls and T3Ls, respectively, are linked to both tissue inflammation and fibrosis, but how their spatial positioning influences beneficial or pathological organ remodeling remains unclear. Using mouse models of liver injury and fibrosis, three-dimensional microscopy, and spatial transcriptomics, we found an accumulation of periportal and fibrotic tract T2Ls, predominantly group 2 innate lymphoid cells (ILC2s), positioned near T3Ls and niche adventitial fibroblasts and adjacent to discrete profibrotic myofibroblasts. Unexpectedly, T2L ablation worsened both carbon tetrachloride– and bile duct ligation–induced liver fibrosis, accompanied by increased IL-17A<sup>+</sup> T3Ls, predominantly γδ T cells. In contrast, concurrent T2L and T3L ablation reduced liver fibrosis. Our work suggests a spatially associated cross-talk between liver lymphocytes and fibroblast niches that tunes liver repair but can go awry in pathological liver fibrosis.</p>}},
  author       = {{Sbierski-Kind, Julia and Cautivo, Kelly M. and Nilsson, Julia and Wagner, Johanna C. and Dahlgren, Madelene W. and Crystal, Nathan Ewing and McClave, Maria and Mroz, Nicholas M. and Ganslmeier, Marlene and Lizama, Carlos O. and Gan, Anna Lu and Matatia, Peri R. and Taruselli, Marcela T. and Chang, Anthony A. and Caryotakis, Sofia and O’Leary, Claire E. and Kotas, Maya and Lee, Jun Hoe and Gu, Taeeun and Seo, Hyeewon and Kim, Hyun Je and Mattis, Aras N. and Peng, Tien and Locksley, Richard M. and Molofsky, Ari B.}},
  issn         = {{2375-2548}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{11}},
  pages        = {{1--21}},
  publisher    = {{American Association for the Advancement of Science (AAAS)}},
  series       = {{Science Advances}},
  title        = {{Type 2 lymphocytes restrict type 3 lymphocytes during liver fibrosis and colocalize in fibroblast niches}},
  url          = {{http://dx.doi.org/10.1126/sciadv.aea6805}},
  doi          = {{10.1126/sciadv.aea6805}},
  volume       = {{12}},
  year         = {{2026}},
}