Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer’s Disease Patients

Contini, Cristina; Serrao, Simone; Manconi, Barbara; Olianas, Alessandra; Iavarone, Federica; Guadalupi, Giulia; Messana, Irene; Castagnola, Massimo; Masullo, Carlo; Bizzarro, Alessandra; Turck, Christoph W.; Maccarrone, Giuseppina; Cabras, Tiziana

doi:10.3390/life13030748

Cited by 2 publications

(1 citation statement)

References 71 publications

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“…It is interesting to highlight that ARPC4, cathepsin G, cystatins B and D, mucin 5B, PIP, and S100A9 were also characterized in another salivary interactome that was associated with cystatin B. It was previously investigated in salivary samples from healthy subjects and patients affected by Alzheimer's disease [35]. Their constant presence in these multifunctional multiprotein complexes suggests their basal role in the protein defense network of the mouth.…”

Section: Cystatin D-c 26 Interactors and Ppis Peculiar To Ctrlsmentioning

confidence: 99%

Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study

Serrao,

Contini,

Guadalupi

et al. 2023

IJMS

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Mastocytosis, a rare blood disorder characterized by the proliferation of clonal abnormal mast cells, has a variegated clinical spectrum and diagnosis is often difficult and delayed. Recently we proposed the cathepsin inhibitor cystatin D-R26 as a salivary candidate biomarker of systemic mastocytosis (SM). Its C26 variant is able to form multiprotein complexes (mPCs) and since protein–protein interactions (PPIs) are crucial for studying disease pathogenesis, potential markers, and therapeutic targets, we aimed to define the protein composition of the salivary cystatin D-C26 interactome associated with SM. An exploratory affinity purification-mass spectrometry method was applied on pooled salivary samples from SM patients, SM patient subgroups with and without cutaneous symptoms (SM+C and SM−C), and healthy controls (Ctrls). Interactors specifically detected in Ctrls were found to be implicated in networks associated with cell and tissue homeostasis, innate system, endopeptidase regulation, and antimicrobial protection. Interactors distinctive of SM−C patients participate to PPI networks related to glucose metabolism, protein S-nitrosylation, antibacterial humoral response, and neutrophil degranulation, while interactors specific to SM+C were mainly associated with epithelial and keratinocyte differentiation, cytoskeleton rearrangement, and immune response pathways. Proteins sensitive to redox changes, as well as proteins with immunomodulatory properties and activating mast cells, were identified in patients; many of them were involved directly in cytoskeleton rearrangement, a process crucial for mast cell activation. Although preliminary, these results demonstrate that PPI alterations of the cystatin D-C26 interactome are associated with SM and provide a basis for future investigations based on quantitative proteomic analysis and immune validation.

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Section: Cystatin D-c 26 Interactors and Ppis Peculiar To Ctrlsmentioning

confidence: 99%

Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study

Serrao,

Contini,

Guadalupi

et al. 2023

IJMS

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Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade

Bergeron,

Dos Santos,

Sitterle

et al. 2024

Nat Commun

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The efficacy and side effects of radiotherapy (RT) depend on parameters like dose and the volume of irradiated tissue. RT induces modulations of the tumor immune microenvironment (TIME) that are dependent on the dose. Low dose RT (LDRT, i.e., single doses of 0.5–2 Gy) has been shown to promote immune infiltration into the tumor. Here we hypothesize that partial tumor irradiation combining the immunostimulatory/non-lethal properties of LDRT with cell killing/shrinkage properties of high dose RT (HDRT) within the same tumor mass could enhance anti-tumor responses when combined with immunomodulators. In models of colorectal and breast cancer in immunocompetent female mice, partial irradiation (PI) with millimetric precision to deliver LDRT (2 Gy) and HDRT (16 Gy) within the same tumor induces substantial tumor control when combined with anti-PD1. Using flow cytometry, cytokine profiling and single-cell RNA sequencing, we identify a crosstalk between the TIME of the differentially irradiated tumor volumes. PI reshapes tumor-infiltrating CD8+ T cells into more cytotoxic and interferon-activated phenotypes but also increases the infiltration of pro-tumor neutrophils driven by CXCR2. The combination of the CXCR2 antagonist SB225002 with PD1 blockade and PI improves tumor control and mouse survival. Our results suggest a strategy to reduce RT toxicity and improve the therapeutic index of RT and immune checkpoint combinations.

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Characterization of Cystatin B Interactome in Saliva from Healthy Elderly and Alzheimer’s Disease Patients

Cited by 2 publications

References 71 publications

Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study

Salivary Cystatin D Interactome in Patients with Systemic Mastocytosis: An Exploratory Study

Non-homogenous intratumor ionizing radiation doses synergize with PD1 and CXCR2 blockade

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