Biology subjects

Park, K. J.

Publications and source records attributed to Park, K. J..

4 recordsLinked to original sources

bioRxiv2026

The anatomical compartment defines distinct immune remodeling within human visceral adipose tissue during aging

Age-associated inflammation varies across tissues, but whether distinct visceral adipose tissue (VAT) depots undergo inflammatory remodeling in a depot-specific manner remains unclear. Here we profiled human peri-organ VAT, comparing kidney-associated fat (KF, from kidney transplantation donors) and gallbladder-associated fat (GBF, from asymptomatic cholecystectomy patients with incidental polyps), using single-cell RNA sequencing, flow cytometry, intracellular protein profiling and in situ analysis. GBF showed broad tissue-residency and granzyme K-associated remodeling across conventional, regulatory and innate-like lymphocyte compartments, whereas KF showed stronger B cell remodeling, greater myeloid representation and more compartmentalized changes within resident effector-like CD8+ T cell states. We further identified age-associated CD20+ T cells with features consistent with local B-T cell interaction and an antigen-experienced, granzyme K-associated inflammatory memory phenotype. In situ analysis revealed age-associated myeloid accumulation and crown-like structure remodeling, accompanied by distinct myeloid inflammatory programs in KF and GBF. Finally, depot-specific immune signatures associated with clinical indices of adjacent kidney and liver function. These findings indicate that age-associated distinct immune programs within peri-organ VAT depots track with local tissue context and the state of the adjacent organ.

immunology↗

bioRxiv2024

Bacterium secretes chemical inhibitor that sensitizes competitor to bacteriophage infection

To overtake competitors, microbes produce and secrete secondary metabolites that kill neighboring cells and sequester nutrients. This natural product-mediated competition likely evolved in complex microbial communities that included viral pathogens. From this ecological context, we hypothesized that microbes secrete metabolites that "weaponize" natural pathogens (i.e., bacteriophages) to lyse their competitors. Indeed, we discovered a bacterial secondary metabolite that sensitizes other bacteria to phage infection. We found that this metabolite provides the producer (a Streptomyces sp.) with a fitness advantage over its competitor (Bacillus subtilis) by promoting phage infection. The phage-promoting metabolite, coelichelin, sensitized B. subtilis to a wide panel of lytic phages, and it did so by preventing the early stages of sporulation through iron sequestration. Beyond coelichelin, other natural products may provide phage-mediated competitive advantages to their producers--either by inhibiting sporulation or through yet-unknown mechanisms.

microbiology↗

bioRxiv2020

E prostanoid receptor 4 expressing macrophages promote the regeneration of the intestinal epithelial barrier upon inflammation

Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of resolution of inflammation but the mechanisms underlying their mucosal healing capacity remains elusive. Here, we describe a subset of E prostanoid receptor 4 (EP4) expressing intestinal macrophages with mucosal healing properties both in human and mice. Notably, Csf1r-iCre EP4-fl/fl mice showed defective mucosal healing and intestinal epithelial barrier regeneration in a dextran sodium sulfate-induced colitis model. Mechanistically, an increased mucosal level of prostaglandin E2 (PGE2) triggers the secretion of chemokine (C-X-C motif) ligand 1 (CXCL1) in monocyte-derived EP4+ macrophages via MAPKs. Subsequently, CXCL1 drives epithelial cell differentiation and proliferation from regenerating crypts during the resolution phase of colitis. Thus, EP4+ intestinal macrophages are essential for the support of the intestinal stem cell niche and for the regeneration of the injured epithelium. One Sentence SummaryProstaglandin E2 licenses E-type prostanoid receptor 4 intestinal macrophage regenerative capacity promoting mucosal healing via the secretion of CXCL1

immunology↗

bioRxiv2018

Unraveling Tumor-Immune Heterogeneity in Advanced Ovarian Cancer Uncovers Immunogenic Effect of Chemotherapy

In metastatic cancer, the role of heterogeneity at the tumor-immune microenvironment, its molecular underpinnings and clinical relevance remain largely unexplored. To understand tumor-immune dynamics at baseline and upon chemotherapy treatment, we performed unbiased pathway and cell type-specific immunogenomics analysis of treatment-naive (38 samples from 8 patients) and paired chemotherapy treated (80 paired samples from 40 patients) high-grade serous ovarian cancer (HGSOC) samples. Whole transcriptome analysis and image-based quantification of T cells from treatment-naive tumors revealed ubiquitous variability in immune signaling and distinct immune microenvironments co-existing within the same individuals and within tumor deposits at diagnosis. To systematically explore cell type composition of the tumor microenvironment using bulk mRNA, we derived consensus immune and stromal cell gene signatures by intersecting state-of-the-art deconvolution methods, providing improved accuracy and sensitivity when compared to HGSOC immunostaining and leukocyte methylation data sets. Cell-type deconvolution and pathway analyses revealed that Myc and Wnt signaling associate with immune cell exclusion in untreated HGSOC. To evaluate the effect of chemotherapy on the intrinsic tumor-immune heterogeneity, we compared site-matched and site-unmatched tumors before and after neoadjuvant chemotherapy. Transcriptomic and T-cell receptor sequencing analyses showed that site-matched samples had increased cytotoxic immune activation and oligoclonal expansion of T cells after chemotherapy, which was not seen in site-unmatched samples where heterogeneity could not be accounted for. These results demonstrate that the tumor-immune interface in advanced HGSOC is intrinsically heterogeneous, and thus requires site-specific analysis to reliably unmask the impact of therapy on the tumor-immune microenvironment.

cancer biology↗