Tissue-specific heterogeneity of Human T follicular helper cells marked by unique transcriptomes and regulatory architecture
Year: 2023
Type: conference-abstract
Abstract: T follicular helper (TFH) cells represent a distinct lineage of CD4 T cells that engage with cognate B cells, facilitating the production of high affinity vaccine- and pathogen-specific antibodies. In humans, TFH cells can be detected in several tissues throughout the body, each representing a unique cellular environment complete with distinct signaling molecules. Despite TFH cell importance to human health, it remains unclear if and how anatomical location results in diversity among TFH cells. Here, we detail tissue-specific heterogeneity of human TFH cells reflected in both transcriptome and chromatin architecture. TFH cells sourced from circulating peripheral blood (cTFH), lung lymph nodes (lnTFH), tonsils (tTFH), and an in vitro differentiation model (exTFH), were subjected to RNA-sequencing and ATAC-sequencing. When comparing expression of conical TFH genes, including BCL6 and PDCD1, a spectrum in magnitude emerged: cTFH < exTFH < lnTFH < tTFH. Increased chromatin accessibility at proximal cis-regulatory elements occurred within the loci of TFH genes in a similar tissue-dependent fashion and correlated with transcript levels. Additionally, unique gene signatures were detected in each TFH population, including the presence of distinct transcription factor networks, implying tissue specific TFH functionality. Integrating PageRank and scRNA-seq of tTFH cells revealed BCL-6, ASCL2, TOX, TOX2, and AIOLOS as potential regulators of the TFH gene program. Collectively, these findings detail tissue specific diversity amongst human TFH cells, while highlighting key developmental networks which could influence the design of future immunological therapies targeting TFH cells. Supported by grants from NIH: (RO1 AI113021, F32 AI161857)
Source: The Journal of Immunology
Institution: Emory University
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4385695649