Follicular T-helper cells articles from across Nature Portfolio

T follicular helper (Tfh) cells contribute to systemic autoimmunity. However, their involvement in the pathology of lupus nephritis (LN) remains unexplored. Here, by combining single-cell analysis of LN patient tissues and humanized mouse models, the authors show that mesangial cell-derived lactate regulates Tfh cell differentiation in LN by promoting Bcl6 lactylation and subsequent stabilization via K6 and k-29-linked polyubiquitination.

SARS-CoV-2 evolves into new subtypes necessitating further vaccine development. Here the authors generate a trivalent vaccine with Receptor Binding Domains from Delta, BA.5 and XBB.1.5 variants and characterize immunogenicity and protection in mice and safety in a phase I vaccine trial in humans.

Mudd, Ellebedy and colleagues integrate single-cell transcriptomics and TCR sequencing to characterize the spike-specific CD4⁺ T_FH cell response in the lymph nodes and blood of BNT162b2-vaccinated and SARS-CoV-2-infected individuals up to 6 months after vaccination or infection.

Schattgen et al. profiled the subsets and clonality of CD4⁺ T_FH cells in the blood and lymph nodes of human volunteers who received two influenza vaccines 1 year apart to characterize their dynamics and clonal evolution over 2 years.

Most subsets of CD4⁺ T-follicular helper cells occur in blood and tonsils, but location enforces specific gene expression. One subtype reveals a cytotoxic phenotype, is circulating or extrafollicular, oligoclonal and shares TCRs with other clusters.

Bob1 manages ICOS and cellular respiration in Tfh cells, ensuring the sustained generation of specific humoral responses. This likely contributes to persistent inflammation resulting from recurring allergen exposure.

Besides killing infected or transformed cells, interferon-activated natural killer cells can kill T follicular helper cells and may contribute to poor antibody responses in some individuals infected with SARS-CoV-2.

CD4⁺ T follicular helper (T_FH) cells that develop in response to a range of pathogens share aspects of a common gene signature. However, cytokine environments, rather than pathogen class, shape diversity in programming potential.

Longitudinal sampling of human lymph nodes using fine-needle aspiration after influenza or SARS-CoV-2 vaccination reveals substantial durability and transcriptional reprogramming of follicular helper T cells over time.

Wherry and colleagues describe how anti-PD-1 immunotherapy impacts outcomes of influenza vaccination in patients with cancer, and specifically, how it increases seroconversion and affects quantitative and qualitative aspects of antibodies and follicular T helper cell responses.