A5044844190- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Immune cells in cancer
- T-cell and B-cell Immunology
- Dermatology and Skin Diseases
- Genomics and Chromatin Dynamics
- Immune responses and vaccinations
- IL-33, ST2, and ILC Pathways
- Gut microbiota and health
- RNA Research and Splicing
- Cancer-related molecular mechanisms research
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- NF-κB Signaling Pathways
- Nutrition, Genetics, and Disease
- Cancer, Stress, Anesthesia, and Immune Response
- RNA modifications and cancer
- Stress Responses and Cortisol
- Single-cell and spatial transcriptomics
- Dietary Effects on Health
- Diet and metabolism studies
- Neuropeptides and Animal Physiology
- Immunotherapy and Immune Responses
- Liver Disease Diagnosis and Treatment
National Institute of Allergy and Infectious Diseases
2019-2025
National Institutes of Health
2019-2025
Ludwig-Maximilians-Universität München
2014-2024
Government of the United States of America
2020-2024
University of California, San Diego
2014-2024
Cornell University
2023
Weill Cornell Medicine
2023
Princeton University
2023
Commensals rule the MAITrix Mucosal-associated invariant T (MAIT) cells play an important role in mucosal homeostasis. MAIT recognize microbial small molecules presented by major histocompatibility complex class Ib molecule MR1. are absent germ-free mice, and mechanisms which microbiota control cell development unknown (see Perspective Oh Unutmaz). Legoux et al. show that, of within thymus is governed bacterial product 5-(2-oxopropylideneamino)-6- d -ribitylaminouracil, rapidly traffics from...
The immune system has evolved in the face of microbial exposure. How maternal infection experienced at distinct developmental stages shapes offspring remains poorly understood. Here, we show that during pregnancy, maternally restricted can have permanent and tissue-specific impacts on immunity. Mechanistically, interleukin-6 produced response to directly impose epigenetic changes fetal intestinal epithelial stem cells, leading long-lasting homeostasis. As a result, previously infected dams...
The microbiota plays a fundamental role in regulating host immunity. However, the processes involved initiation and regulation of immunity to remain largely unknown. Here, we show that skin promotes discrete expression defined endogenous retroviruses (ERVs). Keratinocyte-intrinsic responses ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator interferon genes protein (STING) signaling promoted induction commensal-specific T cells. Inhibition ERV reverse transcription significantly...
Abstract Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention both and microbiota by performing post hoc analysis clinical trial in which each 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ). Using multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic metagenomic datasets,...
Males and females exhibit profound differences in immune responses disease susceptibility. However, the factors responsible for sex tissue immunity remain poorly understood. Here, we uncovered a dominant role type 2 innate lymphoid cells (ILC2s) shaping sexual dimorphism within skin. Mechanistically, negative regulation of ILC2s by androgens leads to reduction dendritic cell accumulation activation males, along with reduced immunity. Collectively, our results reveal androgen-ILC2-dendritic...
Significance Tissues exposed to the environment are sites of exposure symbiotic microbes including fungi that continuously sensed by immune system. Here, we show immunity commensal skin can significantly aggravate tissue inflammation. Enhanced pathology caused preexposure depends on lymphocytes able produce cytokine IL-17 and formation extracellular traps neutrophils. We also found fungal prior experimental modeling psoriasis recapitulates features transcriptional landscape human lesional...
Immune checkpoint inhibitors (ICIs) are essential components of the cancer therapeutic armamentarium. While ICIs have demonstrated remarkable clinical responses, they can be accompanied by immune-related adverse events (irAEs). These inflammatory side effects unclear etiology and impact virtually all organ systems, with most common being sites colonized microbiota such as skin gastrointestinal tract. Here, we establish a mouse model commensal bacteria-driven irAEs demonstrate that immune...
The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. roles of sensory neurons in controlling the adaptive system, more specifically immunity to microbiota, however, remain elusive. Here, we identified a mechanism for direct neuroimmune communication between commensal-specific T lymphocytes mediated by neuropeptide calcitonin gene–related peptide (CGRP) skin. Intravital imaging revealed that are close...
Although macrophages can be polarized to distinct phenotypes in vitro with individual ligands, vivo they encounter multiple signals that control their varied functions homeostasis, immunity, and disease. Here, we identify roles of Rev-erb nuclear receptors regulating responses mouse complex tissue damage wound repair. Rather than reinforcing a specific program macrophage polarization, Rev-erbs repress subsets genes are activated by TLR IL4, TGFβ, damage-associated molecular patterns (DAMPS)....
The cross-talk between the microbiota and immune system plays a fundamental role in control of host physiology. However, tissue-specific factors controlling this dialogue remain poorly understood. Here we demonstrate that T cell responses to commensal colonization are associated with development organized cellular clusters within skin epithelium. These lymphocyte surrounded by keratinocytes expressing discrete program antigen presentation antimicrobial defense. Notably, IL-22–mediated...
Abstract Mechanisms by which members of the AP-1 family transcription factors play non-redundant biological roles despite recognizing same DNA sequence remain poorly understood. To address this question, here we investigate molecular functions and genome-wide binding patterns in primary immortalized mouse macrophages. ChIP-sequencing shows overlapping distinct profiles for each factor that were remodeled following TLR4 ligation. Development a machine learning approach jointly weighs hundreds...