Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin

Ian C. Boothby, Maxime J. Kinet, Devi P. Boda, Elaine Y. Kwan, Sean Clancy, Jarish N. Cohen, Ireneusz Habrylo, Margaret M. Lowe, Mariela Pauli, Ashley E. Yates, Jamie D. Chan, Hobart W. Harris, Isaac M. Neuhaus, Timothy H. McCalmont, Ari B. Molofsky and Michael D. Rosenblum ()
Additional contact information
Ian C. Boothby: University of California at San Franscisco
Maxime J. Kinet: University of California at San Franscisco
Devi P. Boda: University of California at San Franscisco
Elaine Y. Kwan: University of California at San Franscisco
Sean Clancy: University of California at San Franscisco
Jarish N. Cohen: University of California at San Franscisco
Ireneusz Habrylo: University of California at San Franscisco
Margaret M. Lowe: University of California at San Franscisco
Mariela Pauli: University of California at San Franscisco
Ashley E. Yates: University of California at San Franscisco
Jamie D. Chan: University of California at San Franscisco
Hobart W. Harris: University of California at San Franscisco
Isaac M. Neuhaus: University of California at San Franscisco
Timothy H. McCalmont: University of California at San Franscisco
Ari B. Molofsky: University of California at San Franscisco
Michael D. Rosenblum: University of California at San Franscisco

Nature, 2021, vol. 599, issue 7886, 667-672

Abstract: Abstract Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility1. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (TH2) cells within a distinct microanatomical niche. TH2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as TH2-interacting fascial fibroblasts (TIFFs), which expand in response to TH2 cytokines to form subcutaneous fibrous bands. Activation of the TH2–TIFF niche due to neonatal inflammation primes the skin for altered reparative responses to wounding. Furthermore, we identify fibroblasts in healthy human skin that express the TIFF transcriptional signature and detect these cells at high levels in eosinophilic fasciitis, an orphan disease characterized by inflammation and fibrosis of the skin fascia. Taken together, these data define a previously unidentified TH2 cell niche in skin and functionally characterize a disease-associated fibroblast population. The results also suggest a mechanism of immunological priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells to establish an immunological set-point in tissues that is maintained throughout life.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-021-04044-7 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:599:y:2021:i:7886:d:10.1038_s41586-021-04044-7

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-021-04044-7

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().