About

Welcome to the Bando Lab! Innate lymphocytes are professional cytokine-secreting cells that reside in mucosal barrier tissues. These cells make critical contributions to lymphoid tissue development, gut epithelial cell homeostasis, and the host response to pathogens. Our lab uses mouse genetics to investigate how innate lymphocytes are behaviorally controlled by their spatial organization within the gastrointestinal tract and by interactions with adaptive immune cells. We also study how these and other intestinal innate immune cells contribute to tissue development and host defense in neonatal mice.

Research topics

• Biology
• Immunology
• Ecology
• Cell biology
• Microbiology
• Biochemistry
• Neuroscience

Selected publications

• Characterization of NKp46+CCR6+ ILC3s in non-C57BL/6 mice 4352

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Type 3 innate lymphoid cells produce cytokines that maintain intestinal epithelial cell homeostasis, initiate lymphoid tissue development, and enhance host defense mechanisms against extracellular pathogens. Here, we report an ILC3 phenotype characterized by co-expression of NKp46 and CCR6, which we observed in multiple inbred and outbred mouse strains but was notably absent in C57BL/6 mice. NKp46+CCR6+ ILC3s were present in intestinal lamina propria and were confirmed to be innate lymphocytes, developing in the absence of Rag1 but requiring the common gamma chain receptor subunit. Cultures of purified ILC3 subpopulations demonstrated that NKp46+CCR6+ cells were closely related to NKp46+CCR6- ILC3s, which was further confirmed in vivo by tracking adoptively transferred cells. Functionally, NKp46+CCR6+ ILC3s produced more IL-22 on a per cell basis than their NKp46+CCR6- counterparts during both homeostatic and infection conditions, indicating a heightened cell activation state in NKp46+CCR6+ cells. This study reveals an additional RORgt+ ILC3 phenotype, which may be tuned to meet the needs of the intestinal mucosa. Funding Sources Supported by NIH DK118110; T32GM00820; and the Donald E. and Delia B. Baxter Foundation. Topic Categories Mucosal and Regional Immunology (MUC)

  PublisherOA PDFDOI

• An intraepithelial ILC1-like natural killer cell subset produces IL-13

  Frontiers in Immunology · 2025-03-06 · 1 citations

  articleOpen access

  Natural killer (NK) cells are innate immune effectors with considerable heterogeneity and potent antitumor capabilities. Intraepithelial ILC1 (ieILC1)-like NK cells, a population of cytotoxic tissue-resident innate lymphoid cells, have recently been documented in the microenvironment of head and neck squamous cell carcinomas (HNSCC) and other solid tumors. These cells have antitumor cytolytic potential and are potent producers of type 1 cytokines, including IFNγ. Here, we identify a subpopulation of ex vivo differentiated ieILC1-like NK cells that produce IL-13 upon stimulation. Functional characterization revealed that these cells co-expressed IFNγ and IL-13 while maintaining an ILC1 transcriptional signature. IL-13 was induced either upon co-culture with tumor cell lines, or in response to TGF-β and IL-15. IL-13-expressing ieILC1-like NK cells were identified among tumor infiltrating lymphocytes expanded from patient HNSCC tumors, in support of their in vivo existence in primary tumors. These data demonstrate additional heterogeneity within the ieILC1-like NK cell population than previously appreciated and highlight a unique form of ILC plasticity in which cells with clear ILC1 transcriptional profiles express a type 2 cytokine. With the known roles of IL-13 in cancer cell growth dynamics and immunoregulation, the identification of this subset within tumor microenvironments presents a potential target for therapeutic manipulation.

  PublisherOA PDFDOI

• TREM2 deficiency reprograms intestinal macrophages and microbiota to enhance anti–PD-1 tumor immunotherapy

  Science Immunology · 2024-05-17 · 41 citations

  articleOpen access

  The gut microbiota and tumor-associated macrophages (TAMs) affect tumor responses to anti–programmed cell death protein 1 (PD-1) immune checkpoint blockade. Reprogramming TAM by either blocking or deleting the macrophage receptor triggering receptor on myeloid cells 2 (TREM2) attenuates tumor growth, and lack of functional TREM2 enhances tumor elimination by anti–PD-1. Here, we found that anti–PD-1 treatment combined with TREM2 deficiency in mice induces proinflammatory programs in intestinal macrophages and a concomitant expansion of Ruminococcus gnavus in the gut microbiota. Gavage of wild-type mice with R. gnavus enhanced anti–PD-1–mediated tumor elimination, recapitulating the effect occurring in the absence of TREM2. A proinflammatory intestinal environment coincided with expansion, increased circulation, and migration of TNF-producing CD4 + T cells to the tumor bed. Thus, TREM2 remotely controls anti–PD-1 immune checkpoint blockade through modulation of the intestinal immune environment and microbiota, with R. gnavus emerging as a potential probiotic agent for increasing responsiveness to anti-PD-1.

  PublisherOA PDFDOI

• Abstract 3615: TREM2+ macrophages mediate immunosuppression in tumors

  Cancer Research · 2022-06-15

  article

  Abstract Checkpoint immunotherapy unleashes T cell control of tumors, but is undermined by immunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellular signals that sustain microglial responses during Alzheimer’s disease. TREM2 is also expressed by tumor-infiltrating macrophages. Here, we found that Trem2-/- mice are more resistant to growth of various cancers than wild-type mice and are more responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2 mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seq revealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressing immunostimulatory molecules that promote improved T cell responses. TREM2 was expressed in tumor macrophages in over 200 human cancer cases and inversely correlated with prolonged survival for two types of cancer. Thus, TREM2 might be targeted to modify tumor myeloid infiltrates and augment checkpoint immunotherapy. Citation Format: Martina Molgora, Blanda Di Luccia, Darya Khantakova, Natalia Jaeger, Rafael Sanguinetti Czepielewski, Cristiane Secca da Silva, Jennifer Bando, Susan Gilfillan, Marina Cella, Robert Schreiber, Marco Colonna. TREM2+ macrophages mediate immunosuppression in tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3615.

  PublisherDOI

• Ornithine decarboxylase supports ILC3 responses in infectious and autoimmune colitis through positive regulation of IL-22 transcription

  Proceedings of the National Academy of Sciences · 2022 · 40 citations

  • Biology
  • Immunology
  • Microbiology

  infection, which was associated with a decrease in anti-microbial peptide production by the intestinal epithelium. Furthermore, in a model of anti-CD40 colitis, deficiency of ODC1 in ILC3s markedly reduced the production of IL-22 and severity of inflammatory colitis. We conclude that ILC3-intrinsic polyamine biosynthesis facilitates efficient defense against enteric pathogens as well as exacerbates autoimmune colitis, thus representing an attractive target to modulate ILC3 function in intestinal disease.

  PublisherOA PDFDOI

• Whole-genome profiling of DNA methylation and hydroxymethylation identifies distinct regulatory programs among innate lymphocytes

  Nature Immunology · 2022-03-24 · 28 citations

  articleOpen access
  PublisherOA PDFDOI

• The aryl hydrocarbon receptor instructs the immunomodulatory profile of a subset of Clec4a4⁺eosinophils unique to the small intestine

  Proceedings of the National Academy of Sciences · 2022-06-02 · 25 citations

  articleOpen access

  Significance Eosinophils contribute to type 2 immunity against helminths and allergens. The small intestine harbors eosinophils with incompletely understood pathophysiological roles. Here, we show that intestinal eosinophils include two subsets. One expresses the inhibitory receptor Clec4a4 and the inhibitory ligand PD-L1 and is unique to the small intestine; the other manifests a proinflammatory phenotype. Both subsets are blood derived. Remarkably, Clec4a4 + eosinophils were instructed by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that imprints many gut immune cells. Selective AHR deletion in eosinophils depleted Clec4a4 + eosinophils, augmented innate lymphocytes producing type 2 cytokines, and enhanced helminth clearance. We conclude that Clec4a4 + eosinophils have immunomodulatory functions, which could be harnessed for the therapy of food allergies and eosinophilic gastrointestinal disorders.

  PublisherOA PDFDOI

• Indole-3-Carbinol–Dependent Aryl Hydrocarbon Receptor Signaling Attenuates the Inflammatory Response in Experimental Necrotizing Enterocolitis

  ImmunoHorizons · 2021-04-01 · 28 citations

  articleOpen access

  Abstract Necrotizing enterocolitis (NEC) causes significant morbidity and mortality in premature infants; therefore, the identification of therapeutic and preventative strategies against NEC remains a high priority. The ligand-dependent transcription factor aryl hydrocarbon receptor (AhR) is well known to contribute to the regulation of intestinal microbial communities and amelioration of intestinal inflammation. However, the role of AhR signaling in NEC is unclear. Experimental NEC was induced in 4-d-old wild-type mice or mice lacking AhR expression in the intestinal epithelial cells or AhR expression in CD11c+ cells (AhRΔCD11c) by subjecting animals to twice daily hypoxic stress and gavage feeding with formula supplemented with LPS and enteric bacteria. During NEC, compared with wild-type mice treated with vehicle, littermates treated with an AhR proligand, indole-3-carbinol, had reduced expression of Il1b and Marco, a scavenger receptor that mediates dendritic cell activation and the recognition and clearance of bacterial pathogens by macrophages. Furthermore, indole-3-carbinol treatment led to the downregulation of genes involved in cytokine and chemokine, as revealed by pathway enrichment analysis. AhR expression in the intestinal epithelial cells and their cre-negative mouse littermates were similarly susceptible to experimental NEC, whereas AhRΔCD11c mice with NEC exhibited heightened inflammatory responses compared with their cre-negative mouse littermates. In seeking to determine the mechanisms involved in this increased inflammatory response, we identified the Tim-4− monocyte–dependent subset of macrophages as increased in AhRΔCD11c mice compared with their cre-negative littermates. Taken together, these findings demonstrate the potential for AhR ligands as a novel immunotherapeutic approach to the management of this devastating disease.

  PublisherOA PDFDOI

• Spatial distribution of LTi-like cells in intestinal mucosa regulates type 3 innate immunity

  Proceedings of the National Academy of Sciences · 2021-06-03 · 22 citations

  articleOpen access

  Significance The lymphoid tissue inducer (LTi)-like cell is a specialized innate lymphocyte that produces cytokines that promote intestinal epithelial barrier integrity and protective immunity against pathogenic bacteria. Here, we report that the spatial positioning of LTi-like cells within intestinal mucosa enables them to receive signals that control their activity. Deletion of the LTi-like cell chemokine receptor CXCR5 displaced LTi-like cells from their natural niche in gut mucosa and enhanced their capacity to produce cytokines upon activation. LTi-like cell hyperresponsiveness in Cxcr5 -deficient mice strongly improved gut barrier integrity and protected mice during infection with the human opportunistic pathogen Clostridium difficile . Our findings demonstrate that the specialized positioning of LTi-like cells within the gut mucosa controls their activity and impacts protective immunity.

  PublisherOA PDFDOI

• Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders

  Science · 2021 · 439 citations

  • Biology
  • Neuroscience
  • Ecology

  The meninges contain adaptive immune cells that provide immunosurveillance of the central nervous system (CNS). These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for hematopoiesis. B cells reach the meninges from the calvaria through specialized vascular connections. This calvarial-meningeal path of B cell development may provide the CNS with a constant supply of B cells educated by CNS antigens. Conversely, we show that a subset of antigen-experienced B cells that populate the meninges in aging mice are blood-borne. These results identify a private source for meningeal B cells, which may help maintain immune privilege within the CNS.

  PublisherOA PDFDOI

Recent grants

• Immune Checkpoints for Intestinal Innate Lymphoid Cells

  NIH · $182k · 2019–2021

Frequent coauthors

• Marco Colonna

  Hope Center for Neurological Disorders

  52 shared

• Marina Cella

  Washington University in St. Louis

  43 shared

• Susan Gilfillan

  Washington University in St. Louis

  43 shared

• Richard M. Locksley

  University of California, San Francisco

  32 shared

• David Allan

  National Heart Lung and Blood Institute

  29 shared

• James R. Carlyle

  29 shared

• Rodney D. Newberry

  Washington University in St. Louis

  28 shared

• Christina Song

  28 shared

Labs

• Bando LabPI