Biology subjects

Shapiro, H.

Publications and source records attributed to Shapiro, H..

3 recordsLinked to original sources

bioRxiv2025

Langerhans Cells Regulate Tongue Intraepithelial Innervation in a Microbiota- and Age-Dependent Manner

Oral Langerhans cells (LCs) are well recognized for their immunological roles, but their involvement in other physiological processes remains poorly understood. This study identifies a novel function of oral LCs in regulating tongue epithelial innervation. Postnatal LC development coincides with the establishment of local innervation, and LC depletion impairs innervation and alters nociceptive responses, underscoring their neuroimmune function. This function is driven by LC-derived IL-1{beta}, which stimulates basal epithelial cells to produce nerve growth factor (NGF), thereby promoting sensory nerve growth. Transcriptomic analyses revealed neuronal-related pathways enriched in LCs. Aging reduces LC frequency, NGF expression, and epithelial innervation, linking neuroimmune regulation to epithelial aging. While LC frequencies in the tongue remain unaffected in germ-free mice, the microbiota is essential for optimal LC function and NGF production. These findings expand our understanding of oral LCs, revealing their pivotal role in epithelial innervation beyond immune surveillance.

immunology↗

bioRxiv2023

IL-15 priming alters IFN-γ regulation in murine NK cells

Natural killer (NK) effector functions can be triggered by inflammatory cytokines and engagement of activating receptors. NK cell production of IFN-{gamma}, an important immunoregulatory cytokine, exhibits activation-specific IFN-{gamma} regulation. Resting murine NK cells exhibit activation-specific metabolic requirements for IFN-{gamma} production, which are reversed for activating receptor-mediated stimulation following IL-15 priming. While both cytokine and activating receptor stimulation leads to similar IFN-{gamma} protein production, only cytokine stimulation upregulates Ifng transcript, suggesting that protein production is translationally regulated after receptor stimulation. Based on these differences in IFN-{gamma} regulation, we hypothesized that ex vivo IL-15 priming of murine NK cells allows a switch to IFN-{gamma} transcription upon activating receptor engagement. Transcriptional analysis of primed NK cells compared to naive cells or cells cultured with low-dose IL-15 demonstrated that primed cells strongly upregulated Ifng transcript following activating receptor stimulation. This was not due to chromatin accessibility changes in the Ifng locus or changes in ITAM signaling, but was associated with a distinct transcriptional signature induced by ITAM stimulation of primed compared to naive NK cells. Transcriptional analyses identified a common signature of c-Myc (Myc) targets associated with Ifng transcription. While Myc marked NK cells capable of Ifng transcription, Myc itself was not required for Ifng transcription using a genetic model of Myc deletion. This work highlights altered regulatory networks in IL-15 primed cells, resulting in distinct gene expression patterns and IFN-{gamma} regulation in response to activating receptor stimulation.

immunology↗

bioRxiv2019

Aging-associated alterations in the mammary gland revealed by single-cell RNA sequencing

Aging of the mammary gland is closely associated with increased susceptibility to diseases such as cancer, but there have been limited systematic studies of aging-induced alterations within this organ. We performed high-throughput single-cell RNA-sequencing (scRNA-seq) profiling of mammary tissues from young and old nulliparous mice, including both epithelial and stromal cell types. Our analysis identified altered proportions and distinct gene expression patterns in numerous cell populations as a consequence of the aging process, independent of parity and lactation. In addition, we detected a subset of luminal cells that express both hormone-sensing and alveolar markers and decrease in relative abundance with age. These data provide a high-resolution landscape of aging mammary tissues, with potential implications for normal tissue functions and cancer predisposition.

cell biology↗