The staphylococcal protease SspA perturbs the epidermal barrier and promotes IL-22-driven inflammation in allergen-exposed skin
8 affiliations
- 1Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129
- 2International Research Center for Medical Sciences, Kumamoto University, Kumamoto 860-0811, Japan
- 3Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115
- 4Unidad Académica Multidisciplinaria Reynosa Aztlán, Universidad Autónoma de Tamaulipas, Reynosa, Tamaulipas 88740, Mexico
- 5Department of Molecular Biosciences, University of South Florida, Tampa, FL 33620
- 6Center for Antimicrobial Resistance, University of South Florida, Tampa, FL 33620
- 7Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138
- 8Broad Institute of MIT and Harvard, Cambridge, MA 02142
Abstract
Skin colonization by Staphylococcus aureus has emerged as a common feature of atopic dermatitis and other allergic diseases, yet it remains unclear how this bacterium contributes to inflammation and pathology. Our S. aureus secretome analysis and bioactivity-guided fractionation uncover that the serine protease SspA destroys keratinocyte junctions, increases epidermal permeability, and activates an epithelial inflammatory program linked to barrier dysfunction. SspA and house dust mite extract (HDM), when epicutaneously applied in combination, cause interleukin (IL)-22-dependent atopic dermatitis-like skin disease in mice. Spatial single-cell analysis and immunophenotyping of lesional skin of these mice reveal massive elongation and branching of epidermal nerve fibers and the formation of T cells simultaneously producing IL-13 and IL-22. Chemical denervation and the resultant dismantling of the neuroimmune signaling network reverse the pathology driven by SspA–HDM combination. These findings link S. aureus colonization to barrier perturbation, allergen sensitization, and neurogenic dermatitis.
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BibTeX
@article{jimenezandrade2026staphylococcal,
title = {{The staphylococcal protease SspA perturbs the epidermal barrier and promotes IL-22-driven inflammation in allergen-exposed skin}},
author = {Yanek Jiménez-Andrade and Stefano Sol and Toshimi Yoshida and Miles Tran and Lilah Gmyrek and Kathryn R. Hillette and Juan A. Vazquez-Mora and Juan M. Jiménez-Andrade and Lindsey N. Shaw and Katia Georgopoulos and Anna Mandinova and Kevin Wei and Ethan A. Lerner and Jin Mo Park},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2611563123},
url = {https://doi.org/10.1073/pnas.2611563123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The staphylococcal protease SspA perturbs the epidermal barrier and promotes IL-22-driven inflammation in allergen-exposed skin
AU - Yanek Jiménez-Andrade
AU - Stefano Sol
AU - Toshimi Yoshida
AU - Miles Tran
AU - Lilah Gmyrek
AU - Kathryn R. Hillette
AU - Juan A. Vazquez-Mora
AU - Juan M. Jiménez-Andrade
AU - Lindsey N. Shaw
AU - Katia Georgopoulos
AU - Anna Mandinova
AU - Kevin Wei
AU - Ethan A. Lerner
AU - Jin Mo Park
PY - 2026
DA - 2026/10/28
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2611563123
UR - https://doi.org/10.1073/pnas.2611563123
AB - Skin colonization by Staphylococcus aureus has emerged as a common feature of atopic dermatitis and other allergic diseases, yet it remains unclear how this bacterium contributes to inflammation and pathology. Our S. aureus secretome analysis and bioactivity-guided fractionation uncover that the serine protease SspA destroys keratinocyte junctions, increases epidermal permeability, and activates an epithelial inflammatory program linked to barrier dysfunction. SspA and house dust mite extract (HDM), when epicutaneously applied in combination, cause interleukin (IL)-22-dependent atopic dermatitis-like skin disease in mice. Spatial single-cell analysis and immunophenotyping of lesional skin of these mice reveal massive elongation and branching of epidermal nerve fibers and the formation of T cells simultaneously producing IL-13 and IL-22. Chemical denervation and the resultant dismantling of the neuroimmune signaling network reverse the pathology driven by SspA–HDM combination. These findings link S. aureus colonization to barrier perturbation, allergen sensitization, and neurogenic dermatitis.
SN - 0027-8424
SN - 1091-6490
ER -