Katherine Nico

All Publications

• Distinct epigenomic landscapes underlie tissue-specific memory T cell differentiation. Immunity Buquicchio, F. A., Fonseca, R., Yan, P. K., Wang, F., Evrard, M., Obers, A., Gutierrez, J. C., Raposo, C. J., Belk, J. A., Daniel, B., Zareie, P., Yost, K. E., Qi, Y., Yin, Y., Nico, K. F., Tierney, F. M., Howitt, M. R., Lareau, C. A., Satpathy, A. T., Mackay, L. K. 2024

  Abstract

  The memory CD8+ T cell pool contains phenotypically and transcriptionally heterogeneous subsets with specialized functions and recirculation patterns. Here, we examined the epigenetic landscape of CD8+ T cells isolated from seven non-lymphoid organs across four distinct infection models, alongside their circulating T cell counterparts. Using single-cell transposase-accessible chromatin sequencing (scATAC-seq), we found that tissue-resident memory T (TRM) cells and circulating memory T (TCIRC) cells develop along distinct epigenetic trajectories. We identified organ-specific transcriptional regulators of TRM cell development, including FOSB, FOS, FOSL1, and BACH2, and defined an epigenetic signature common to TRM cells across organs. Finally, we found that although terminal TEX cells share accessible regulatory elements with TRM cells, they are defined by TEX-specific epigenetic features absent from TRM cells. Together, this comprehensive data resource shows that TRM cell development is accompanied by dynamic transcriptome alterations and chromatin accessibility changes that direct tissue-adapted and functionally distinct T cell states.

  View details for DOI 10.1016/j.immuni.2024.06.014

  View details for PubMedID 39043184

• Tuft cells mediate commensal remodeling of the small intestinal antimicrobial landscape. Proceedings of the National Academy of Sciences of the United States of America Fung, C., Fraser, L. M., Barrón, G. M., Gologorsky, M. B., Atkinson, S. N., Gerrick, E. R., Hayward, M., Ziegelbauer, J., Li, J. A., Nico, K. F., Tyner, M. D., DeSchepper, L. B., Pan, A., Salzman, N. H., Howitt, M. R. 2023; 120 (23): e2216908120

  Abstract

  Succinate produced by the commensal protist Tritrichomonas musculis (T. mu) stimulates chemosensory tuft cells, resulting in intestinal type 2 immunity. Tuft cells express the succinate receptor SUCNR1, yet this receptor does not mediate antihelminth immunity nor alter protist colonization. Here, we report that microbial-derived succinate increases Paneth cell numbers and profoundly alters the antimicrobial peptide (AMP) landscape in the small intestine. Succinate was sufficient to drive this epithelial remodeling, but not in mice lacking tuft cell chemosensory components required to detect this metabolite. Tuft cells respond to succinate by stimulating type 2 immunity, leading to interleukin-13-mediated epithelial and AMP expression changes. Moreover, type 2 immunity decreases the total number of mucosa-associated bacteria and alters the small intestinal microbiota composition. Finally, tuft cells can detect short-term bacterial dysbiosis that leads to a spike in luminal succinate levels and modulate AMP production in response. These findings demonstrate that a single metabolite produced by commensals can markedly shift the intestinal AMP profile and suggest that tuft cells utilize SUCNR1 and succinate sensing to modulate bacterial homeostasis.

  View details for DOI 10.1073/pnas.2216908120

  View details for PubMedID 37253002

• Succinate and tuft cells: how does this sensory process interface with food allergy? The Journal of allergy and clinical immunology Nico, K. F., Tyner, M. D., Howitt, M. R. 2022

  View details for DOI 10.1016/j.jaci.2022.07.016

  View details for PubMedID 35934085