Biology subjects

Lim, A. I.

Publications and source records attributed to Lim, A. I..

5 recordsLinked to original sources

bioRxiv2026

Lactation Remodels the Maternal Lung to Promote Preemptive Innate Defense

Lactation is a hallmark of mammalian evolution, imposing extraordinary physiological demands on mothers to nourish their offspring. Yet how mothers maintain their own health while meeting these demands remains poorly understood. Here, we discover that lactation establishes a preemptive innate defense program in the maternal lung through enhanced epithelial production of surfactant proteins and mucin, vascular remodeling that supports granulocyte recruitment and accumulation of activated intravascular neutrophils. These tissue-wide adaptations safeguard lactating dams against diverse respiratory pathogens. We further identify prolactin and CGRP as neuroendocrine signals contributing to pulmonary remodeling and uncover parallel lactation-associated granulocyte adaptations in marsupial and non-human primate models. Together, our findings expand the framework of reproductive immunology, revealing that reproduction couples systemic fetal tolerance with tissue-specific immune adaptations that safeguard maternal health during lactation.

immunology↗

bioRxiv2025

Deep Learning of Functional Perturbations from Condensate Morphology

Biomolecular condensates compartmentalize the interior of living cells to spatiotemporally organize complex functions, yet linking molecular interactions within condensates to their mesoscale organization remains a major challenge. To bridge this gap, we developed a neural network-based framework - Deep-Phase - that uses microscopy images to quantitatively classify condensate morphology changes resulting from pharmacological alterations in associated biochemical processes. We use Deep-Phase to precisely quantify time- and concentration-dependent structural perturbations to the multiphase nucleolus and show that they are tightly coupled to potencies of drugs inhibiting rRNA transcription and processing. Applying Deep-Phase in a chemical screen, we identify a unique nucleolar morphology and discover a role for a DNA topoisomerase in rRNA processing. Mechanistic studies of this morphology provide insights into how interfaces between nucleolar subcompartments are maintained. We demonstrate Deep-Phases adaptability to diverse cell lines, labels, and condensates, offering a powerful platform for uncovering cellular organizing principles and therapeutic targets. HighlightsO_LIA deep learning framework, Deep-Phase, classifies and quantifies drug-induced changes in morphologies of nucleoli, nucleolar speckles, and viral cytoplasmic condensates, directly from images. C_LIO_LITime- and concentration-dependent morphological responses to perturbation predict associated disruptions in RNA transcription and processing. C_LIO_LIUsing Deep-Phase in a high-content small molecule screen reveals a unique nucleolar morphology induced by TOP1 inhibition. C_LIO_LITOP1 inhibition leads to reduced levels and processing of large ribosomal subunit precursors and provides a mechanism for maintenance of nucleolar phase boundaries. C_LI

molecular biology↗

bioRxiv2024

The ontogeny of immune tolerance: a model of the early-life gut microbiome and adaptive immunity

To achieve immune and microbial homeostasis during adulthood, the developing immune system must learn to identify which microbes to tolerate and which to defend against. How such immune education unfolds remains a major knowledge gap. We address this gap by synthesizing existing literature to develop a mechanistic mathematical model representing the interplay between gut ecology and adaptive immunity in early life. Our results indicate that the inflammatory tone of the microenvironment is the mediator of information flow from pre- to post-weaning periods. We evaluate the power of postnatal fecal samples for predicting immunological trajectories and explore breastfeeding scenarios when maternal immunological conditions affect breastmilk composition. Our work establishes a quantitative basis for immune education, yielding insights into questions of applied relevance.

immunology↗

bioRxiv2023

The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota

The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. The roles of sensory neurons in controlling the adaptive immune system, and more specifically immunity to the microbiota, however, remain elusive. Here, we identified a novel mechanism for direct neuroimmune communication between commensal-specific T lymphocytes and somatosensory neurons mediated by the neuropeptide Calcitonin Gene-Related Peptide (CGRP) in the skin. Intravital imaging revealed that commensal-specific T cells are in close proximity to cutaneous nerve fibers in vivo. Correspondingly, we observed upregulation of the receptor for the neuropeptide CGRP, RAMP1, in CD8+ T lymphocytes induced by skin commensal colonization. Neuroimmune CGRP-RAMP1 signaling axis functions in commensal-specific T cells to constrain Type 17 responses and moderate the activation status of microbiota-reactive lymphocytes at homeostasis. As such, modulation of neuroimmune CGRP-RAMP1 signaling in commensal-specific T cells shapes the overall activation status of the skin epithelium, thereby impacting the outcome of responses to insults such as wounding. The ability of somatosensory neurons to control adaptive immunity to the microbiota via the CGRP-RAMP1 axis underscores the various layers of regulation and multisystem coordination required for optimal microbiota-reactive T cell functions under steady state and pathology. Significance statementMultisystem coordination at barrier surfaces is critical for optimal tissue functions and integrity, in response to microbial and environmental cues. In this study, we identified a novel neuroimmune crosstalk mechanism between the sensory nervous system and the adaptive immune response to the microbiota, mediated by the neuropeptide CGRP and its receptor RAMP1 on skin microbiota-induced T lymphocytes. The neuroimmune CGPR-RAMP1 axis constrains adaptive immunity to the microbiota and overall limits the activation status of the skin epithelium, impacting tissue responses to wounding. Our study opens the door to a new avenue to modulate adaptive immunity to the microbiota utilizing neuromodulators, allowing for a more integrative and tailored approach to harnessing microbiota-induced T cells to promote barrier tissue protection and repair.

immunology↗

bioRxiv2021

Maternal infection promotes offspring tissue-specific immune fitness

The mammalian immune system has evolved in the face of microbial exposure. How maternal infection experienced at distinct developmental stages shapes the offspring immune system remains poorly understood. Here we show that during pregnancy, maternally restricted infection can have permanent and tissue-specific impacts on offspring immunity. Mechanistically, maternal IL-6 produced in response to infection can specifically and directly impose epigenetic changes on fetal intestinal epithelial cells. Such imprinting is associated with long-lasting impacts on intestinal immune homeostasis, characterized by enhanced tonic immunity to the microbiota and heightened Th17 responses within the gut, but not at other barrier sites. Furthermore, the offspring from IL-6-exposed dams developed enhanced protective immunity to gastrointestinal infection. Together, this work demonstrates that maternal infection experienced during pregnancy can be coopted by the fetus to promote long-term tissue-specific fitness. Summary sentenceInfection-induced maternal IL-6 impacts offspring epithelial cells, resulting in heightened immunity to the microbiota and pathogens.

immunology↗