Biology subjects

Gallo, R. L.

Publications and source records attributed to Gallo, R. L..

5 recordsLinked to original sources

bioRxiv2026

Disease context dictates the cellular targets of IL-17 in inflammatory skin disease

Therapeutic blockade of IL-17 and TNF can effectively treat inflammatory skin diseases such as hidradenitis suppurativa and psoriasis, yet the relative importance of the different cell types that respond to IL-17 and TNF remains unresolved. Keratinocytes are viewed as the dominant effector cells, whereas fibroblasts have recently emerged as important contributors. In mice, topical imiquimod induces IL-17- and TNF-dependent skin inflammation and is frequently used to model psoriasis. Here, we demonstrate that intradermal injection of recombinant IL-17 and TNF elicits skin inflammation with features of hidradenitis suppurativa, including a gene expression program that is distinct from psoriasis and imiquimod-induced inflammation. Single-cell transcriptomic network analysis identified dermal fibroblasts as the dominant cell communication hub in hidradenitis suppurativa and in mice injected with IL-17 and TNF. In contrast, fibroblasts and keratinocytes both show strong network involvement in psoriasis and in mice challenged with imiquimod. Cell-type-specific deletion of IL-17 receptor A in mice revealed that imiquimod-induced inflammation depends equally on IL-17 signaling in fibroblasts and keratinocytes, whereas inflammation induced by intradermal IL-17 and TNF only requires fibroblasts to recognize IL-17 and is independent of keratinocyte IL-17 sensing. Single-cell transcriptomic analysis of these conditional knockout mice further demonstrated that keratinocytes and fibroblasts activate divergent and disease-dependent transcriptional programs following activation by IL-17. Together, these findings introduce a new conceptual framework wherein IL-17 signaling is routed through distinct cellular and molecular pathways depending on disease context and establish complementary experimental systems for interrogating type 17 skin inflammation.

immunology↗

bioRxiv2026

Multi-omics Analyses of Facial Skin in Acne Identify Distinct Microbial and Metabolic Features at Lesional and Non-lesional Sites

The microbial and biochemical landscape of clinically normal-appearing skin in individuals with acne remains uncharacterized. Here, we performed longitudinal multi-omics profiling of facial skin from 10 individuals with moderate acne and 10 healthy controls, integrating 16S rRNA gene sequencing, shotgun metagenomics, and untargeted metabolomics across lesional and non-lesional sites. Compositional tensor factorization revealed that non-lesional acne skin occupies a distinct intermediate state between healthy and lesional skin in both the microbiome and the metabolome. Machine learning models distinguished healthy from non-lesional acne skin with 70% accuracy, demonstrating that molecular dysbiosis occurs in areas of the skin without visible lesions. Non-lesional sites exhibited reduced microbial diversity, strain-level shifts in Corynebacterium and Lawsonella correlating with disease severity, and metabolic alterations, including elevated lipids and perturbed amino acid and dipeptide profiles. Microbe-metabolite co-occurrence network analyses revealed that healthy skin is enriched for protective metabolites such as urocanic acid, while acne-associated skin shows distinct co-occurrence patterns. These findings establish that acne represents a field effect disorder, with molecular alterations extending beyond visible lesions to encompass the entire facial skin ecosystem. This molecular signature of pre-lesional skin provides potential biomarkers for early intervention and suggests that effective acne treatment may require holistic approaches targeting the broader skin environment rather than individual lesions alone.

microbiology↗

bioRxiv2024

Positionally distinct interferon stimulated dermal immune acting fibroblasts promote neutrophil recruitment in Sweet's syndrome

Sweets syndrome is a poorly understood inflammatory skin disease characterized by neutrophil infiltration to the dermis. Single-nucleus and bulk transcriptomics of archival clinical samples of Sweets syndrome revealed a prominent interferon signature in Sweets syndrome skin that was reduced in tissue from other neutrophilic dermatoses. This signature was observed in different subsets of cells, including fibroblasts that expressed interferon-induced genes. Functionally, this response was supported by analysis of cultured primary human dermal fibroblasts that were observed to highly express neutrophil chemokines in response to activation by type I interferon. Furthermore, single-molecule resolution spatial transcriptomics of skin in Sweets syndrome identified positionally distinct immune acting fibroblasts that included a CXCL1+ subset proximal to neutrophils and a CXCL12+ subset distal to the neutrophilic infiltrate. This study defines the cellular landscape of neutrophilic dermatoses and suggests dermal immune acting fibroblasts play a role in the pathogenesis of Sweets syndrome through recognition of type I interferons.

immunology↗

bioRxiv2021

Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius.

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. Fluorescence and electron microscopy revealed that S. felis antimicrobials disrupted bacterial but not eukaryotic cell membranes. LC/MS identified several S. felis phenol-soluble modulin beta (PSM{beta}) peptides that exhibited antimicrobial and anti-inflammatory activity. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.

microbiology↗

bioRxiv2019

Obesity Potentiates TH2 Immunopathology via Dysregulation of PPAR

How obesity affects immune function is not well understood. Clinically, obesity is strongly associated with severe TH2 immunopathology1-3, though the physiological, cellular, and molecular underpinnings of this association remain obscure. Here, we demonstrate that obese mice are susceptible to severe atopic dermatitis (AD), a major manifestation of TH2 immunopathology and disease burden in humans4,5. Mechanistically, we show that dysregulation of the nuclear hormone receptor (NHR) PPAR{gamma} (peroxisome proliferator-activated receptor gamma) in T cells is a causal link between obesity and the increased TH2 immunopathology. We find that PPAR{gamma} oversees a cellular metabolic transcriptional program that restrains nuclear gene expression of the chief TH2 priming and effector cytokine interleukin-4 (IL-4). Accordingly, thiazolidinediones (TZDs), potent PPAR{gamma} agonists, robustly protect obese mice from TH2 immunopathology. Collectively, these findings establish PPAR{gamma} as a molecular link between obesity and TH2 immune homeostasis and identify TZDs as novel therapeutic candidates for TH2 immunopathology. Fundamentally, these findings demonstrate that shifting physiologic metabolic states can shape the tone of adaptive immune responses to modulate differential disease susceptibility.

immunology↗