About

Juan J. Lafaille, PhD, is a professor in the Department of Cell Biology and the Department of Pathology at NYU Grossman School of Medicine. His research focuses on the molecular pathogenesis of autoimmune and allergic diseases, cancer, and immunology. His laboratory uses transgenic and knockout mice to study the molecular mechanisms responsible for the normal control of T-lymphocyte reactivity and the changes that occur when T-lymphocytes become either aggressive against self antigens or inappropriately reactive against environmental substances. Currently, his work includes examining the development of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, in transgenic mice bearing anti-myelin basic protein (MBP) T-lymphocytes, and investigating factors controlling the synthesis of interleukins involved in asthma, such as IL-4 and IL-5, and the increased production of immunoglobulin E.

Research topics

• Biology
• Medicine
• Immunology
• Biochemistry
• Microbiology
• Internal medicine
• Endocrinology
• Cell biology

Selected publications

• Functional border-associated macrophages limit Alzheimer’s Disease progression

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-02-03 · 1 citations

  articleOpen accessSenior authorCorresponding

  Abstract Brain-resident macrophages are known to play numerous roles in the progression of Alzheimer’s Disease (AD). However, the relative contribution of microglia and border-associated macrophages (BAM) to AD pathogenesis has been difficult to disentangle. We recently identified Maf , a newly described AD GWAS gene, as essential for BAM, but not microglial, survival. By crossing BAM depleted mice with the 5xFAD AD model, we found stark evidence of cerebral amyloid angiopathy (CAA), increased overall β-amyloid burden, accelerated markers of neurodegeneration, and early memory deficits. In the healthy brain, BAM take up more β-amyloid per cell than microglia. However, as disease progresses, both in human AD patient samples and model AD mice, BAM number is reduced, and the remaining BAMs display impaired endocytic capacity, and show signs of metabolic exhaustion at an earlier age than microglia. Thus, strategies to preserve or restore BAM function represents a novel therapeutic avenue for AD and CAA.

  PublisherDOI

• <span>Functional Border-Associated Macrophages Limit Alzheimer’s Disease Progression</span>

  SSRN Electronic Journal · 2025-01-01

  preprintOpen access
  PublisherDOI

• A Developmental Role for Microglial Presenilin 1 in Memory

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-01-27 · 1 citations

  preprintOpen access

  Summary Microglia, the macrophages of the brain, are increasingly recognized to play a key role in synaptic plasticity and function; however, the underlying mechanisms remain elusive. Presenilin 1 (PS1) is an essential protein involved in learning and memory, through neuronal mechanisms. Loss of Presenilin function in neurons impairs synapse plasticity and causes cognitive deficits in mice. Surprisingly, here we show memory enhancement in mice by deleting PS1 selectively in microglia. We further demonstrate increased synapse transmission and in vivo neuronal activity in mice by depleting PS1 during microglial development, but not after microglial maturation. Remarkably, conditional deletion of PS1 in microglia during development increased memory retention in adulthood and was dependent on the NMDA receptor subunit GluN2B. In vivo calcium imaging of freely behaving mice revealed increased amplitude of neuronal Ca2+ transients in the CA1 hippocampus of PS1 cKO mice compared to control mice, suggesting a greater CA1 engagement during novel object exploration. Finally, loss of PS1 in microglia mitigated synaptic and cognitive deficits in a mouse model of Alzheimer’s disease. Together our results reveal a novel mechanism and function of PS1 in microglia in which modulation can enhance neuronal activity, learning and memory in mice.

  PublisherOA PDFDOI

• Learning‐dependent dendritic spine plasticity is impaired in spontaneous autoimmune encephalomyelitis

  Developmental Neurobiology · 2021-05-05 · 15 citations

  article

  Cognitive impairment is often observed in multiple sclerosis and its animal models, experimental autoimmune encephalomyelitis (EAE). Using mice with immunization-induced EAE, we have previously shown that the stability of cortical synapses is markedly decreased before the clinical onset of EAE. In this study, we examined learning-dependent structural synaptic plasticity in a spontaneous EAE model. Transgenic mice expressing myelin basic protein-specific T cell receptor genes develop EAE spontaneously at around 8 weeks of age. Using in vivo two-photon microscopy, we found that the elimination and formation rates of postsynaptic dendritic spines in somatosensory and motor cortices increased weeks before detectable signs of EAE and remained to be high during the disease onset. Despite the elevated basal spine turnover, motor learning-induced spine formation was reduced in presymptomatic EAE mice, in line with their impaired ability to retain learned motor skills. Additionally, we found a substantial elevation of IFN-γ mRNA in the brain of 4-week-old presymptomatic mice, and treatment of anti-IFN-γ antibody reduced dendritic spine elimination in the cortex. Together, these findings reveal synaptic instability and failure to form new synapses after learning as early brain pathology of EAE, which may contribute to cognitive and behavioral deficits seen in autoimmune diseases.

  PublisherDOI

• Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-03-01 · 2 citations

  preprintOpen access

  ABSTRACT In the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they generate new oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet which induces widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.

  PublisherOA PDFDOI

• c-MAF dependent perivascular macrophages regulate diet induced metabolic syndrome

  bioRxiv (Cold Spring Harbor Laboratory) · 2021-02-08 · 4 citations

  preprintOpen accessSenior authorCorresponding

  SUMMARY Macrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues and appear to play a role in development and disease processes, although it remains unclear what are the key features of these cells. Here, we identify a subpopulation of perivascular macrophages in several organs, characterized by their dependence on the transcription factor c-MAF, displaying non-conventional macrophage markers including LYVE1, Folate receptor 2 and CD38. Conditional deletion of c-MAF in macrophage lineages caused ablation of perivascular macrophages in the brain and altered muscularis macrophages program in the intestine. In the white adipose tissue (WAT), c-MAF deficient perivascular macrophages displayed an altered gene expression profile, which was linked to an increased vascular branching into the tissue. Upon feeding on high fat diet (HFD), mice with c-MAF deficient macrophages showed improved metabolic parameters compared to wild-type mice, including less weight gain, greater glucose tolerance and reduced inflammatory cell profile in WAT. These results define c-MAF as a central regulator of perivascular macrophages cell identity and transcriptional program in vivo and reveal a novel role for this tissue resident macrophage population in the regulation of metabolic syndrome.

  PublisherOA PDFDOI

• Food colorants metabolized by commensal bacteria promote colitis in mice with dysregulated expression of interleukin-23

  Cell Metabolism · 2021 · 97 citations

  • Biology
  • Immunology
  • Microbiology
  PublisherOA PDFDOI

• Transcriptomic analysis of loss of Gli1 in neural stem cells responding to demyelination in the mouse brain

  Scientific Data · 2021-10-28 · 6 citations

  articleOpen access

  In the adult mammalian brain, Gli1 expressing neural stem cells reside in the subventricular zone and their progeny are recruited to sites of demyelination in the white matter where they generate new oligodendrocytes, the myelin forming cells. Remarkably, genetic loss or pharmacologic inhibition of Gli1 enhances the efficacy of remyelination by these neural stem cells. To understand the molecular mechanisms involved, we performed a transcriptomic analysis of this Gli1-pool of neural stem cells. We compared murine NSCs with either intact or deficient Gli1 expression from adult mice on a control diet or on a cuprizone diet which induces widespread demyelination. These data will be a valuable resource for identifying therapeutic targets for enhancing remyelination in demyelinating diseases like multiple sclerosis.

  PublisherOA PDFDOI

• c-MAF–dependent perivascular macrophages regulate diet-induced metabolic syndrome

  Science Immunology · 2021-10-01 · 65 citations

  articleSenior authorCorresponding

  Macrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues and appear to play a role in development and disease processes, although it remains unclear what the key features of these cells are. Here, we identify a subpopulation of perivascular macrophages in several organs, characterized by their dependence on the transcription factor c-MAF and displaying nonconventional macrophage markers including LYVE1, folate receptor 2, and CD38. Conditional deletion of c-MAF in macrophage lineages caused ablation of perivascular macrophages in the brain and altered muscularis macrophages program in the intestine. In the white adipose tissue (WAT), c-MAF–deficient perivascular macrophages displayed an altered gene expression profile, which was linked to an increased vascular branching. Upon feeding high-fat diet (HFD), mice with c-MAF–deficient macrophages showed improved metabolic parameters compared with wild-type mice, including less weight gain, greater glucose tolerance, and reduced inflammatory cell profile in WAT. These results define c-MAF as a central regulator of the perivascular macrophage transcriptional program in vivo and reveal an important role for this tissue-resident macrophage population in the regulation of metabolic syndrome.

  PublisherDOI

• Spleen plays a major role in DLL4-driven acute T-cell lymphoblastic leukemia

  Theranostics · 2020-12-16 · 6 citations

  articleOpen access

  DLL4 expression in human leukemic cells can be a source of Notch activity in T-ALL, and the spleen plays a major role in a genetic mouse model of DLL4-driven T-ALL.

  PublisherDOI

Recent grants

• NIH Grant R01AI045654

  NIH · $1.5M · 2006

• NIH Grant R56AI088553

  NIH · $423k · 2011

• NIH Grant R56AI041647

  NIH · $821k · 2011

• Cellular and molecular mechanisms of IgE cell memory in allergic responses

  NIH · $2.9M · 2017–2023

• NIH Grant R01AI041647

  NIH · $3.0M · 2008

Frequent coauthors

• Susumu Tonegawa

  Massachusetts Institute of Technology

  283 shared

• Shigeyoshi Itohara

  RIKEN Center for Brain Science

  232 shared

• Marc Bonneville

  Institut Mérieux (France)

  226 shared

• Yohtaroh Takagaki

  University of Washington

  222 shared

• Andrew G. Farr

  University of Washington

  218 shared

• Peter Mombaerts

  Max Planck Research Unit for Neurogenetics

  215 shared

• Ralph T. Kubo

  University of Occupational and Environmental Health Japan

  202 shared

• Charles A. Janeway

  St. John’s Health Sciences Centre

  201 shared

Labs

• Health Tech HubPI