Biology subjects

Srinivasan, T.

Publications and source records attributed to Srinivasan, T..

3 recordsLinked to original sources

bioRxiv2026

A single-cell atlas of intestinal immune cells across the day-night cycle reveals dynamic populations

The small intestine houses an array of immune cells that receive diverse inputs from food intake, microbiota, and other cues that vary by time of day. However, how diurnal variation influences intestinal immune cell proportions and functions is unclear. Here, we use flow cytometry and single cell RNA sequencing to establish an atlas of 815,073 mouse small intestine immune cells at four times across the day-night cycle. These data suggest possible temporal coordination of dendritic cell antigen processing and subsequent T cell antigen recognition. Most cells express circadian clock genes and have intrinsic oscillatory transcriptomes. However, differentiated antibody-producing plasma cells have minimal circadian gene expression and instead may receive extrinsic oscillatory cues from other cell types. Finally, certain populations of B cells are extremely dynamic, with broad transcriptional changes within a six hour time span. This dataset provides insight into the circadian dynamics of intestinal immunity. SummaryO_LIAn atlas of 815,073 small intestine immune cells across four time-points reveals a large proportion of naive B and T cells. C_LIO_LIGene expression profiles suggest coordination of antigen processing in dendritic cells prior to antigen recognition by T cells. C_LIO_LITh17 and innate lymphoid cells have high expression of circadian clock genes and most immune cells have rhythmic gene expression. C_LIO_LIPopulations of certain B cell subtypes, including transitional B cells and centrocytes, are extremely dynamic with large shifts over a six hour time frame. C_LIO_LITerminally differentiated antibody-producing plasma cells have minimal circadian gene expression and few oscillatory genes. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/701519v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@162f451org.highwire.dtl.DTLVardef@1960711org.highwire.dtl.DTLVardef@a9fd4aorg.highwire.dtl.DTLVardef@341f42_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2025

Timing of immune checkpoint blockade shapes anti-tumor immunity via a clock-dependent chemokine axis

Circadian clocks regulate immunity, yet how they shape the tumor immune microenvironment and influence cancer immunotherapy remains unclear. Here, we show that tumor immune infiltration and immune checkpoint inhibitor efficacy vary by time of day in mice, driven by intrinsic clocks in dendritic cells and CD8+ T cells. Time-of-day modulates the abundance, spatial organization, and cytokine-chemokine production of tumor-infiltrating immune cells. Mechanistically, dendritic cell clocks control expression of Cx3cl1, driving recruitment of CX3CR1+CD8+ T cells and thereby reshaping the tumor immune microenvironment to enhance immunotherapy efficacy. Disruption of this axis abolishes time-of-day-dependent differences in treatment response. These findings identify a circadian mechanism of immune cell recruitment to tumors and provide mechanistic insight into clinical observations linking treatment timing to immunotherapy outcomes. One sentence summaryTime of day determines cancer immunotherapy efficacy through a circadian clock-dependent chemokine axis.

immunology↗

bioRxiv2025

The gut microbiota directs vitamin A flux to regulate intestinal T cell development

The intestinal microbiota shapes adaptive immunity, but the mechanisms remain incompletely defined. Here, we show that the microbiota initiates the movement of retinoids--dietary vitamin A derivatives including retinol and retinoic acid--through a sequential pathway from epithelial cells to myeloid cells and ultimately to T cells in the mesenteric lymph nodes (mLNs). This cellular axis is traversed over three days. Microbe-associated molecular patterns (MAMPs) initiate retinoid flux by inducing expression of serum amyloid A (SAA) proteins. These epithelial retinol-binding proteins are necessary and sufficient for epithelial-to-myeloid cell retinoid transfer and for myeloid cell migration to the mLNs. In the mLNs, microbial antigen drives retinoid transfer from myeloid cells to developing T cells, culminating in T cell retinoid uptake and transcriptional programming. This pathway is activated during postnatal development, when gut adaptive immunity is first established. These findings reveal that the microbiota programs intestinal adaptive immunity by regulating immune cell access to a nutrient-derived developmental signal. HighlightsO_LIThe gut microbiota enables vitamin A flux to developing intestinal CD4 T cells. C_LIO_LIMicrobiota-induced SAA initiates vitamin A flux along a gut myeloid-T cell axis. C_LIO_LIMicrobial molecular patterns and antigen drive distinct steps of vitamin A flux. C_LIO_LIMicrobiota-driven vitamin A flux programs intestinal T cell homing and maturation. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=192 HEIGHT=200 SRC="FIGDIR/small/674524v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@13b3906org.highwire.dtl.DTLVardef@11ceee3org.highwire.dtl.DTLVardef@87913forg.highwire.dtl.DTLVardef@50c9a0_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗