About

Lalit Beura is an Assistant Professor of Molecular Microbiology and Immunology at Brown University. His laboratory focuses on understanding how T cells integrate diverse local microbial and environmental stimuli at mucosal sites to shape distinct and dynamic immune processes in health and disease. T cells are a key component of host defense against pathogenic infection in barrier mucosal surfaces, which are common sites of microbial entry. Beura's research aims to develop a more complete understanding of the fundamental biology of T cells in the reproductive mucosae, particularly within the female reproductive tract (FRT). The FRT has evolved to mount a robust anti-pathogen defense while maintaining tolerance towards an immunologically foreign fetus, making it a unique model system for studying T cell adaptation to diverse environmental inputs. His work seeks to inform improved vaccination strategies, develop novel therapies against infection and malignancy, and advance maternal-fetal health.

Research topics

• Biology
• Immunology
• Cell biology
• Virology
• Microbiology

Selected publications

• JoVE Video Dataset

  2026-02-04

  databaseSenior author

  Barrier mucosal tissues play an important role in the differentiation and function of resident T cells. Among the diverse cell populations within these tissues, epithelial cells are key drivers of T cell differentiation. However, our understanding of the epithelial-derived signals that shape T cell biology in mucosal environments remains limited, largely due to a lack of specific tools and the complexity of available model systems. Here, we describe a murine vaginal epithelial organoid-CD8 T cell co-culture system that models dynamic interactions between infected epithelium and virus-specific CD8 T cells. This protocol enables phenotypic and functional analysis of T cell responses within a physiologically relevant three-dimensional epithelial microenvironment. Using this system, we demonstrate the differentiation of effector CD8 T cells into tissue-resident memory T cells (TRM). This versatile in vitro culture system provides reductionist opportunities to investigate molecular details of epithelial cues behind CD8 T cell differentiation that govern protective immunity and immunopathology in barrier organs.

  PublisherDOI

• <em>In Vitro</em> Resident Memory CD8 T Cell Differentiation Using Epithelial Organoid-T Cell Co-culture System

  Journal of Visualized Experiments · 2026-02-03

  articleOpen accessSenior author

  Barrier mucosal tissues play an important role in the differentiation and function of resident T cells. Among the diverse cell populations within these tissues, epithelial cells are key drivers of T cell differentiation. However, our understanding of the epithelial-derived signals that shape T cell biology in mucosal environments remains limited, largely due to a lack of specific tools and the complexity of available model systems. Here, we describe a murine vaginal epithelial organoid-CD8 T cell co-culture system that models dynamic interactions between infected epithelium and virus-specific CD8 T cells. This protocol enables phenotypic and functional analysis of T cell responses within a physiologically relevant three-dimensional epithelial microenvironment. Using this system, we demonstrate the differentiation of effector CD8 T cells into tissue-resident memory T cells (TRM). This versatile in vitro culture system provides reductionist opportunities to investigate molecular details of epithelial cues behind CD8 T cell differentiation that govern protective immunity and immunopathology in barrier organs.

  PublisherOA PDFDOI

• Temporal Dissection of TGF-β signaling reveals differential impact during female reproductive mucosal CD8 resident memory T cell differentiation

  Mucosal Immunology · 2026-02-01

  articleOpen accessSenior author
  PublisherOA PDFDOI

• Protocol for the coculture of murine vaginal epithelial organoids and T cells to induce resident memory CD8 T cell differentiation

  STAR Protocols · 2025-08-29 · 1 citations

  articleOpen accessSenior authorCorresponding

  Inducing robust resident memory T cell (TRM) establishment in mucosal tissues could enhance immunotherapy and vaccine efficacy. However, the factors influencing TRM formation are not fully understood. We present a protocol to coculture murine effector CD8 T cells with epithelial organoids, which serve as a reductionist model for investigating TRM differentiation in vitro . We describe steps for naive CD8 T cell activation, coculture of T cells with vaginal epithelial organoids (VEOs), and analysis of T cell phenotypes via flow cytometry. For complete details on the use and execution of this protocol, please refer to Ulibarri et al. 1 • Steps for activating naive murine CD8 T cells isolated from secondary lymphoid organs • Protocol for CD8 T cell-epithelial organoid coculture to induce TRM differentiation • Guidance on using basement membrane hydrogel and designing coculture media composition Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics. Inducing robust resident memory T cell (TRM) establishment in mucosal tissues could enhance immunotherapy and vaccine efficacy. However, the factors influencing TRM formation are not fully understood. We present a protocol to coculture murine effector CD8 T cells with epithelial organoids, which serve as a reductionist model for investigating TRM differentiation in vitro . We describe steps for naive CD8 T cell activation, coculture of T cells with vaginal epithelial organoids (VEOs), and analysis of T cell phenotypes via flow cytometry.

  PublisherDOI

• IL-12 conditioning and reconditioning of in vitro activated adoptively transferred CD8+ T cells promotes tissue residency and anti-tumor immunity 3981

  The Journal of Immunology · 2025-11-01

  articleOpen access

  Abstract Description The anti-tumor effector functions of in vitro activated tumor-specific CD8+ T lymphocytes (CTL) following adoptive cell transfer (ACT) are well-studied, but less is known about tissue resident memory T cell populations (TRM) formed by ACT. Using multiple murine tumor models and T cell receptor (TCR) transgenic mice, we report that naive T cells activated in vitro by anti-CD3/CD28 in the presence of interleukin-12 (IL-12) robustly populate non-lymphoid tissues (NLT) and adopt canonical TRM phenotypes (CD69+, CD103+, CD49a+) in vivo. Interrogation of these TRM using in vivo assays including parabiosis, alarm therapy, and circulation depletion reveals a key role for ACT derived TRM in tumor protection. To model clinical ACT where isolation of naive tumor-specific T cells is difficult, we reactivated ACT-derived memory CD8+ T cells ex vivo and observed bias toward effector-like circulating memory following in vivo transfer. Use of interleukin-2 (IL-2) to post-expand CTL in vitro prior to ACT dramatically impaired numbers in vivo. While CD69 levels on rare IL-2 expanded CTL populating NLT after ACT appeared normal, expression of CXCR6 and P2RX7 receptors associated with TRM was reduced. Inclusion of IL-12 during reactivation of IL-2 post-expanded CTL restored in vivo expansion and TRM properties, even if IL-12 was absent during initial activation. Enforcing TRM formation and function during in vitro programming may improve the efficacy of CD8+ and other engineered T cells for ACT. Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

  PublisherOA PDFDOI

• Assessing the impact of the vaginal microbiome on reproductive immunity using human ectocervical organoids 3995

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Dysbiotic vaginal microbiome is a principal contributor to increased acquisition of several sexually transmitted infections (STIs) in women. Microbial dysbiosis, marked by a shift in microbial composition toward anaerobic species associated with bacterial vaginosis (BV), can compromise the integrity of the genital epithelium. Local immune cells can further foment this inflammation. However, a molecular understanding of how the microbial-immune-epithelial interactions are regulated is lacking. One major hurdle hindering progress is the lack of suitable in vitro models that accurately replicate the complex and dynamic nature of the in vivo vaginal microenvironment. Here, we have established a human cervical epithelial organoid-based system that can serve as a scaffold to integrate immune cells and microbiome-derived signals to better model the reproductive mucosa. Architecturally, these organoids maintained the stratified structure of the ectocervical epithelium. In response to bacterial metabolites derived from a BV-associated microbe Gardnerella vaginalis, these organoids produced pro-inflammatory cytokines that include IL-1β and TNF-α whereas Lactobacillus crispatus-derived bacterial supernatant didn’t alter these cytokine levels. Introducing immune cells in these organoids will enable mechanistic interrogation of the tripartite interaction among the microbiome, immune cells, and epithelium underlying BV-associated epithelial disruption and consequent susceptibility to STIs. Funding Sources Supported by NIH R01AI177704; NIH R21AI183017 Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• Monocyte-derived TGF-β shapes memory CD8+ T cells

  Cellular and Molecular Immunology · 2025-07-10

  letterSenior author
  PublisherDOI

• Modeling antiviral immune responses across distinct epithelial niches of the female reproductive tract using organoids 4108

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description The female reproductive tract (FRT) is a significant entry point for a number of pathogens, and epithelial cells bordering the FRT mucosa are often pathogens’ initial targets during infection. Epithelium-intrinsic innate immune defenses are crucial to limit initial pathogen replication. Epithelial cells also shape local adaptive immunity and are crucial for establishing robust resident memory T cell (TRM)-mediated immunity. However, our understanding of how the FRT epithelium coordinates antiviral defense is far from complete. This issue is further complicated by the distinct epithelial linings across the FRT: single layer columnar epithelia (type-1 mucosa) line the endometrium and endocervix, while stratified squamous epithelia (type-2 mucosa) border the ectocervix and vagina. Here we established three-dimensional organoids resembling type-1 and -2 mucosa that maintained the architectural characteristics of their respective native epithelia and were susceptible to infection by Herpes simplex virus-1/2. We characterized epithelial innate immune responses upon viral infection as well as the interaction of infected epithelium with effector CD8 T cells. This model also allowed testing of functional capabilities of TRM cells against pathogen challenge in distinct mucosal epithelium. Altogether we established a reductionist platform to conduct mechanistic studies of epithelial immunity and epithelial-T cell interactions in the reproductive mucosa. Funding Sources Supported by: NIH R01 AI177704; NIH R21AI183017 Topic Categories Viral Immunology (VIR)

  PublisherOA PDFDOI

• Differential impact of TGF-ß signaling during distinct stages of mucosal CD8 resident memory T cell differentiation 4388

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Resident memory CD8 T cell (TRM) development progresses through distinct stages comprising of initial activation of naive T cells into effectors in secondary lymphoid organs, trafficking of effectors to target tissue via blood, and final TRM differentiation at the tissue of residence under the influence of the local microenvironment. The cytokine TGF-β has emerged as a central regulator of epithelial TRM formation, but how TGF-β modulates these distinct stages of TRM differentiation is not known. Combining genetic mouse models that limit TGF-β availability or restrict CD8 T cell-specific TGF-β signaling, here we probed the temporal requirement of TGF-β in mucosal TRM formation. Using a murine model of reproductive tract infection, we found that restricting the availability of total or active TGF-β during naive T cell stage didn’t perturb CD8 T cells’ differentiation into TRM. However, abrogation of TGF-β signaling either during effector differentiation or early memory formation significantly reduced epithelial TRM differentiation. Even mature epithelial CD8 TRM cells relied on TGF-β signaling for their continued maintenance. Memory CD8 T cells generated in the absence of TGF-β signaling had altered functional profile after antigenic recall. Taken together, these suggest a stage-specific role of TGF-β in the formation of antiviral mucosal TRM formation with implications for improving vaccination and local immunotherapy approaches. Funding Sources R01 AI177704 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

  PublisherOA PDFDOI

• Vaginal lactobacilli produce anti-inflammatory β-carboline compounds

  Cell Host & Microbe · 2024-10-17 · 39 citations

  articleOpen access
  PublisherOA PDFDOI

Frequent coauthors

• David Masopust

  University of Minnesota

  64 shared

• Vaiva Vezys

  30 shared

• Pamela C. Rosato

  Dartmouth College

  26 shared

• Sathi Wijeyesinghe

  University of Minnesota

  26 shared

• Jason M. Schenkel

  The University of Texas MD Anderson Cancer Center

  20 shared

• Emily A. Thompson

  Spinal Cord Injury BC

  19 shared

• Mohammad H Hasan

  Brown University

  17 shared

• Jason S. Mitchell

  University of Minnesota

  15 shared

Education

• PhD, Veterinary Biomedical Sciences

  University of Nebraska-Lincoln

  2011