All Publications


  • A conserved Bacteroidetes antigen induces anti-inflammatory intestinal T lymphocytes. Science (New York, N.Y.) Bousbaine, D., Fisch, L. I., London, M., Bhagchandani, P., Rezende de Castro, T. B., Mimee, M., Olesen, S., Reis, B. S., VanInsberghe, D., Bortolatto, J., Poyet, M., Cheloha, R. W., Sidney, J., Ling, J., Gupta, A., Lu, T. K., Sette, A., Alm, E. J., Moon, J. J., Victora, G. D., Mucida, D., Ploegh, H. L., Bilate, A. M. 2022; 377 (6606): 660-666

    Abstract

    The microbiome contributes to the development and maturation of the immune system. In response to commensal bacteria, intestinal CD4+ T lymphocytes differentiate into functional subtypes with regulatory or effector functions. The development of small intestine intraepithelial lymphocytes that coexpress CD4 and CD8αα homodimers (CD4IELs) depends on the microbiota. However, the identity of the microbial antigens recognized by CD4+ T cells that can differentiate into CD4IELs remains unknown. We identified β-hexosaminidase, a conserved enzyme across commensals of the Bacteroidetes phylum, as a driver of CD4IEL differentiation. In a mouse model of colitis, β-hexosaminidase-specific lymphocytes protected against intestinal inflammation. Thus, T cells of a single specificity can recognize a variety of abundant commensals and elicit a regulatory immune response at the intestinal mucosa.

    View details for DOI 10.1126/science.abg5645

    View details for PubMedID 35926021

  • Islet cell replacement and transplantation immunology in a mouse strain with inducible diabetes. Scientific reports Bhagchandani, P., Chang, C. A., Zhao, W., Ghila, L., Herrera, P. L., Chera, S., Kim, S. K. 2022; 12 (1): 9033

    Abstract

    Improved models of experimental diabetes are needed to develop cell therapies for diabetes. Here, we introduce the B6 RIP-DTR mouse, a model of experimental diabetes in fully immunocompetent animals. These inbred mice harbor the H2b major histocompatibilitycomplex (MHC), selectively express high affinity human diphtheria toxin receptor (DTR) in islet beta-cells, and are homozygous for the Ptprca (CD45.1) allele rather than wild-type Ptprcb (CD45.2). 100% of B6 RIP-DTR mice rapidly became diabetic after a single dose of diphtheria toxin, and this was reversed indefinitely after transplantation with islets from congenic C57BL/6 mice. By contrast, MHC-mismatched islets were rapidly rejected, and this allotransplant response was readily monitored via blood glucose and graft histology. In peripheral blood of B6 RIP-DTR with mixed hematopoietic chimerism, CD45.2 BALB/c donor bloodimmune cells were readily distinguished from host CD45.1 cells by flow cytometry. Reliable diabetes induction and other properties in B6 RIP-DTR mice provide an important new tool to advance transplant-based studies of islet replacement and immunomodulation to treat diabetes.

    View details for DOI 10.1038/s41598-022-13087-3

    View details for PubMedID 35641781

  • Simultaneous recording and marking of brain microstructures JOURNAL OF NEURAL ENGINEERING Ramadi, K. B., Dagdeviren, C., Bhagchandani, P., Nunez-Lopez, C., Kim, M., Langer, R., Graybiel, A. M., Cima, M. J. 2020; 17 (4): 044001

    Abstract

    The vast majority of techniques to study the physiology of the nervous system involve inserting probes into the brain for stimulation, recording, or sampling. Research is increasingly uncovering the fine microstructure of the brain, each of its regions with dedicated functions. Accurate knowledge of the placement of probes interrogating these regions is critical. We have developed a customizable concentric marking electrode (CME) consisting of an iron core within a 125 μm-stainless steel (SS) sheath for co-localization of targeted regions in the brain. We used a dielectric layer stack of SiO2, Al2O3, SiO2 to electrically encapsulate the iron core and minimize exposure area to avoid significant increases in inflammatory response triggered by the probes. The CME can record multi-neuronal extracellular firing patterns. Appropriate electrical polarity of the iron and SS components controls the deposition of iron microdeposits on brain tissue. We show that in vivo labels by this method can be as small as 100 μm, visible via noninvasive magnetic resonance imaging (MRI) as well as post-mortem histology, and illustrate how deposit size can be tuned by varying stimulus parameters. We targeted the CA3 area of the hippocampus in adult rats and demonstrate that iron microdeposits are remarkably stable and persist up to 10 months post-deposition. Using a single probe for recording and marking avoids inaccuracies with re-insertion of separate probes and utilizes iron microdeposits as valuable fiducial markers in vivo and ex vivo.

    View details for DOI 10.1088/1741-2552/aba161

    View details for Web of Science ID 000555589700001

    View details for PubMedID 32604074