Biology subjects

Ishikawa, E.

Publications and source records attributed to Ishikawa, E..

3 recordsLinked to original sources

bioRxiv2025

A lipid-driven, microbe-independent mechanism of acne via Lrig1+ follicular progenitor cells

Long-chain saturated fatty acids (lcSFAs) are abundant in the skin, but their pathogenic roles in acne remain unclear. In human sebum profiling, C16:0, the most abundant lcSFA, was the only fatty acid significantly elevated in acne and correlated with inflammatory comedone counts. We then established a mouse model that faithfully recapitulates human acne phenotypes, in which topical C16:0 penetrated the epidermis and induced sebocyte hyperplasia, comedogenesis, and follicular inflammation. Mechanistically, C16:0 activated keratinization and inflammatory pathways and drove sebocyte-lineage differentiation from Lrig1+progenitor cells, which function as cutaneous lipid sensors. These effects persisted in germ-free mice and were unaffected by fatty acid transporter modulation, while MyD88 signaling was partially required for inflammatory cell recruitment. Together, our findings identified C16:0 as a human acne-associated lipid that recapitulates disease hallmarks through a microbe-independent, lipid-driven pathway, highlighting Lrig1+cells as central hubs in remodeling of the pilosebaceous unit.

cell biology↗

bioRxiv2023

Early acquisition of S-specific Tfh clonotypes after SARS-CoV-2 vaccination is associated with the longevity of anti-S antibodies

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) {beta} sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as "sustainers"), but not in "decliners". Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic bacteria. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly-responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.

immunology↗

bioRxiv2021

Identification, crystallization and epitope determination of public TCR shared and expanded in COVID-19 patients

T cells play pivotal roles in protective immunity against SARS-CoV-2 infection. Follicular helper T (Tfh) cells mediate the production of antigen-specific antibodies; however, T cell receptor (TCR) clonotypes used by SARS-CoV-2-specific Tfh cells have not been well characterized. Here, we first identified and crystallized public TCR of Tfh clonotypes that are shared and expanded in unhospitalized COVID-19-recovered patients. These clonotypes preferentially recognized SARS-CoV-2 spike (S) protein epitopes which are conserved among emerging SARS-CoV-2 variants. These clonotypes did not react with S proteins derived from common cold human coronaviruses, but cross-reacted with symbiotic bacteria, which might confer the publicity. Among SARS-CoV-2 S epitopes, S864-882, presented by frequent HLA-DR alleles, could activate multiple public Tfh clonotypes in COVID-19-recovered patients. Furthermore, S864-882-loaded HLA tetramer preferentially bound to CD4+ T cells expressing CXCR5. In this study, we identified and crystallized public TCR for SARS-CoV-2 that may contribute to the prevention of COVID-19 aggravation.

immunology↗