Biology subjects

Shakiba, R.

Publications and source records attributed to Shakiba, R..

3 recordsLinked to original sources

bioRxiv2026

A transient CD87-centred axis enhances the Th17 potential of cDC2 in neonates

Type 2 conventional dendritic cells (cDC2) orchestrate T cell immunity, yet the signals that regulate their tissue-specific functions across development remain poorly defined. We demonstrate that splenic cDC2/DC3 subset heterogeneity is established perinatally and that splenic ESAMhi cDC2A undergo a transcriptional and functional transition around the time of weaning, which occurs independently of microbiota. Comparative transcriptomics identified neonatal-specific regulatory programs, including elevated expression of Plaur, encoding CD87/uPAR. CD87 sensitizes neonatal ESAMhi cDC2A to coagulation factor XII (FXII), thereby enhancing their capacity to promote Th17 differentiation. In human infants, CD87 expression was high on cDC2, its expression declined with age and in plasma of preterm infants CD87 positively correlated with Th17-associated cytokines. Together, we identify a conserved link between coagulation pathways and cDC2 developmental programming that may offer new opportunities to modulate Th17 responses in infancy. SummarySplenic cDC2 undergo a transcriptional and functional remodeling around weaning. Elevated CD87 expression on neonatal cDC2 enhances their FXII-driven Th17 potential. Conserved in human infants, elevated CD87 expression reveals a coagulation-linked pathway shaping early-life dendritic cell function and suggests targets to improve vaccination.

immunology↗

bioRxiv2026

Periweaning diet-induced activation of an IFNγ-mediated regulatory circuit promotes the homeostasis of cytotoxic CD8+ T Cells

Balancing pathogen defence with maintaining tolerance to environmental antigens, such as food or commensals, in neonates is essential for survival and the establishment of life-long immune homeostasis. Instructed by environmental signals type 1 conventional dendritic cells (cDC1) drive either T cell tolerance or immunity. Here, we uncover an interferon (IFN)-{gamma}-driven regulatory circuit in early life that relays dietary cues to spleen cDC1. Loss-of-function demonstrates that IFN{gamma}-mediated STAT1-signaling induces an immunogenic maturation program in spleen cDC1 that instructs cDC1 to expand effector memory CD8 T cells. This program emerges during weaning, when IFN{gamma} production from lymphocytes rises, it occurs in germ-free mice and remains responsive to dietary intervention in adult mice. During the transition from breastfeeding to solid food at weaning, this circuit relays dietary information to spleen cDC1 to shape the effector phenotype of food-antigen specific CD8+ T cells in a feed-forward manner, allowing cDC1 to recalibrate the T cell pool at the moment of nutritional independence.

immunology↗

bioRxiv2024

Cross-species analyses reveal RORγt-expressing dendritic cells are a lineage of antigen presenting cells conserved across tissues

Conventional dendritic cells (cDCs) are potent antigen presenting cells (APCs) that exhibit tissue and age-specific diversity allowing them to direct situation-adapted immunity. Thereby they harbor great potential for being targeted in vaccination and cancer. Here, we resolve conflicting data about expression of retinoic acid receptor-related orphan receptor-{gamma}t (ROR{psi}t) in cDCs. We show that ROR{psi}t+ DCs exist in murine lymphoid and non-lymphoid tissues across age. Fate mapping, functional assays and single cell multiomic profiling reveal these cells as ontogenetically and transcriptionally distinct from other well characterized cDC subtypes, as well as from ROR{psi}t+ type 3 innate lymphocytes (ILC3s). We show that ROR{psi}t+ DCs can migrate to lymph nodes and activate naive CD4+ T cells in response to inflammatory triggers. Comparative and cross-species transcriptomics revealed homologous populations in human spleen, lymph nodes and intestines. Further, integrated meta-analyses aligned ROR{psi}t+ DCs identified here with other emerging populations of ROR{psi}t+APCs, including R-DC-like cells, Janus cells/extrathymic Aire expressing cells (eTACs) and subtypes of Thetis cells. While ROR{psi}t+APCs have primarily been linked to T cell tolerance, our work establishes ROR{psi}t+ DCs as unique lineage of immune sentinel cells conserved across tissues and species that expands the functional repertoire of ROR{psi}t+ APCs beyond promoting tolerance. One sentence summaryROR{gamma}t+ DC exhibit versatile APC functions and are a distinct immune lineage conserved across age, tissues and species that entails Thetis cells, Janus cells/ROR{gamma}t+ eTACs and R-DC-like cells.

immunology↗