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| Status |
Public on Oct 01, 2021 |
| Title |
Early Life Inflammation Primes a Th2-Fibroblast Niche in Skin |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Inflammation early in life can prime the local immune milieu of peripheral tissues, causing lasting changes in immunologic tone that confer disease protection or susceptibility. The cellular and molecular mechanisms that incite changes in immune tone in many nonlymphoid tissues remain largely unknown. We find that time-limited neonatal inflammation induced by transient reduction of neonatal regulatory T cells (Tregs) causes a dramatic dysregulation of subcutaneous tissue in murine skin, accompanied by the selective accumulation of Th2 cells within a distinct microanatomic 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 by neonatal inflammation primes skin for altered reparative responses to wounding. We further identify fibroblasts in healthy human skin expressing the TIFF transcriptional signature and find 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 novel Th2 niche in skin, functionally characterize a disease-associated fibroblast population, and suggest a mechanism of immunologic priming whereby inflammation early in life creates networks between adaptive immune cells and stromal cells, establishing an immunological set-point in tissues that is maintained throughout life.
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| Overall design |
Single cell RNAseq of FACS-purified skin stromal cells from mice (P22 control and Treg-depleted) as well as humans (healthy controls and one eosinophilic fasciitis patient).
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| Contributor(s) |
Boothby IC, Kinet MJ, Boda DP, Kwan EY, Clancy S, Cohen JN, Habrylo I, Lowe MM, Pauli M, Kwan EY, Yates AE, Chan JD, Harris HW, Neuhaus IM, McCalmont TH, Molofsky AB, Rosenblum MD |
| Citation(s) |
34707292 |
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| Submission date |
Aug 30, 2021 |
| Last update date |
Nov 01, 2021 |
| Contact name |
Ian Chen Boothby |
| E-mail(s) |
ian.boothby@ucsf.edu
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| Organization name |
University of California San Francisco
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| Lab |
Rosenblum
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| Street address |
513 Parnassus Ave, HSW-1201B
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (2) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA758894 |
| SRA |
SRP334705 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE183031_RAW.tar |
152.7 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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