Kunovac Kallak, T. | bioRxiv Science

bioRxiv2026

Regional epithelial architecture and spatial distribution of T and B lymphocytes in the human fallopian tube

The human fallopian tube plays a critical role in reproduction, yet its structural organization and immune landscape remain incompletely characterized. Here, we analyzed tissue from women of reproductive age across three anatomical regions (isthmus, ampulla, and fimbriae) throughout the menstrual cycle. By using antibody-based imaging together with automated image analysis, the epithelial thickness and spatial distribution of T and B lymphocytes was assessed. No significant differences in epithelial thickness were observed between proliferative and secretory phases. However, significant regional variation was identified, with the epithelium thickest in the isthmus and thinnest in the ampulla. Both CD8A+ T lymphocytes and CD20+ B lymphocytes were present throughout the fallopian tube, with their abundance strongly correlated across patients. Spatial analysis further revealed that both lymphocyte populations were preferentially localized to the mucosal compartment adjacent to the lumen, and intraepithelial B lymphocytes were consistently observed. Together, these findings provide new insight into epithelial organization and immune cell distribution in the human fallopian tube, highlighting the complexity of the tubal immune microenvironment and its potential relevance for reproductive biology.

immunology↗

bioRxiv2024

Switch-like Gene Expression Modulates Disease Susceptibility

A fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five ([~]18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold, p<10-4) and vaginal atrophy (44-fold, p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like gene ALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.

bioinformatics↗