Cited by 60Chemokine receptors and signalingDermatology and Skin DiseasesInflammation biomarkers and pathways
CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17
Open accessCavagnero, Kellen J., Li, Fengwu, Dokoshi, Tatsuya, Nakatsuji, Teruaki, O’Neill, Alan M., Aguilera, Carlos, Liu, Edward, Shia, Michael +3 more·2024·Journal of Experimental Medicine
DOI 10.1084/jem.20231425PMC PMC10890925
Abstract
The skin provides an essential barrier for host defense through rapid action of multiple resident and recruited cell types, but the complex communication network governing these processes is incompletely understood. To define these cell–cell interactions more clearly, we performed an unbiased network analysis of mouse skin during invasive S. aureus infection and revealed a dominant role for CXCL12+ fibroblast subsets in neutrophil communication. These subsets predominantly reside in the reticular dermis, express adipocyte lineage markers, detect IL-17 and TNFα, and promote robust neutrophil recruitment through NFKBIZ-dependent release of CXCR2 ligands and CXCL12. Targeted deletion of Il17ra in mouse fibroblasts resulted in greatly reduced neutrophil recruitment and increased infection by S. aureus. Analogous human CXCL12+ fibroblast subsets abundantly express neutrophil chemotactic factors in psoriatic skin that are subsequently decreased upon therapeutic targeting of IL-17. These findings show that CXCL12+ dermal immune acting fibroblast subsets play a critical role in cutaneous neutrophil recruitment and host defense.
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Non-immune skin cells contribute to barrier defense by maintaining epithelial integrity, producing AMPs, and releasing chemokines to recruit immune effector cells.
“Non-immune skin cells contribute to barrier defense by maintaining epithelial integrity, producing AMPs, and releasing chemokines to recruit immune effector cells [95,96].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [96]
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InfluentialT cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines
Fossiez, F., Djossou, O., Chomarat, P., Flores-Romo, L., Ait-Yahia, S., Maat, C., Pin, J. J., Garrone, P., Garcia, E., Saeland, S., et al. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.183.6.2593 · Cited by 1,526 · cited 1× · see citing works
“These observations in 3T3-L1 cells were consistent with prior reports using mixed primary dermal fibroblasts (Fossiez et al., 1996; Ha et al., 2014) and supported our findings that adipocyte lineage subsets within the heterogenous dermal fibroblast populations can respond to IL-17 by production of…”
The IL-17 Family of Cytokines in Health and Disease
McGeachy, M. J., Cua, D. J., & Gaffen, S. L. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.021 · Cited by 1,443 · see citing works
Innate antimicrobial peptide protects the skin from invasive bacterial infection
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Self-citationIdentification of a mesenchymal progenitor cell hierarchy in adipose tissue
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Neutrophil chemoattractant receptors in health and disease: Double-edged swords
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Dermal adipocytes protect against invasive <i>Staphylococcus aureus</i> skin infection
Zhang, L.-J., Guerrero-Juarez, C. F., Hata, T., Bapat, S. P., Ramos, R., Plikus, M. V., & Gallo, R. L. (2015) · Science · doi:10.1126/science.1260972 · Cited by 471 · see citing works
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Cited by
Sorted by citations
Host–Candida auris interactions in the skin
Thangamani, S., Balakumar, A., Datta, A., Bryak, G., & Lionakis, M. S. (2026) · PLOS Pathogens · doi:10.1371/journal.ppat.1014075 · Cited by 3 · see citing works
- Authors
- Cavagnero, K. J., Li, F., Dokoshi, T., Nakatsuji, T., O’Neill, A. M., Aguilera, C., Liu, E., Shia, M., Osuoji, O., Hata, T., & Gallo, R. L.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Gallo, Richard L.
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2024-02-23
- Volume
- 221
- Issue
- 4
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC10890925
- OpenAlex
- W4392100932
- Cited by
- 60
- References
- 10
- Citations by year
- 2026: 31 · 2025: 19 · 2024: 10
- FWCI
- 10.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
- Funders
- National Institutes of Health (#S10 OD026929, T32DK007202, R01DK121760, R01AR076082, R01AI153185, U01AI152038, P50AR080594, R37AI052453)
- Moores Cancer Center, UC San Diego (CA23100-28)
- National Science Foundation (GRFP2038238)
- Topics
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- neutrophil recruitment, IL-17, host defense, Staphylococcus aureus infection, skin barrier, NF-κB signaling, IL-17RA, psoriasis, intercellular communication
- MeSH terms
- Animals, Fibroblasts, Humans, Skin, Staphylococcus aureus, Interleukin-17, Neutrophil Infiltration, Mice, Chemokine CXCL12
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