Infection and inflammation stimulate expansion of a CD74+ Paneth cell subset to regulate disease progression

Iyshwarya Balasubramanian, Sheila Bandyopadhyay, Juan Flores, Jared Bianchi-Smak, Xiang Lin, Haoran Liu, Shengxiang Sun, Natasha B. Golovchenko, Yue Liu, Dahui Wang, Radha Patel, Ivor Joseph, Panan Suntornsaratoon, Justin Vargas, Peter H.R. Green, Govind Bhagat, Stephen M. Lagana, Wang Ying, Yi Zhang, Zhihan WangWei Vivian Li, Sukhwinder Singh, Zhongren Zhou, George Kollias, Laura A. Farr, Shannon N. Moonah, Shiyan Yu, Zhi Wei, Edward M. Bonder, Lanjing Zhang, Pawel R. Kiela, Karen L. Edelblum, Ronaldo Ferraris, Ta Chiang Liu, Nan Gao

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Paneth cells (PCs), a specialized secretory cell type in the small intestine, are increasingly recognized as having an essential role in host responses to microbiome and environmental stresses. Whether and how commensal and pathogenic microbes modify PC composition to modulate inflammation remain unclear. Using newly developed PC-reporter mice under conventional and gnotobiotic conditions, we determined PC transcriptomic heterogeneity in response to commensal and invasive microbes at single cell level. Infection expands the pool of CD74+ PCs, whose number correlates with auto or allogeneic inflammatory disease progressions in mice. Similar correlation was found in human inflammatory disease tissues. Infection-stimulated cytokines increase production of reactive oxygen species (ROS) and expression of a PC-specific mucosal pentraxin (Mptx2) in activated PCs. A PC-specific ablation of MyD88 reduced CD74+ PC population, thus ameliorating pathogen-induced systemic disease. A similar phenotype was also observed in mice lacking Mptx2. Thus, infection stimulates expansion of a PC subset that influences disease progression.

Original languageEnglish
Article numbere113975
JournalEMBO Journal
Volume42
Issue number21
DOIs
StatePublished - 2 Nov 2023
Externally publishedYes

Keywords

  • CD74
  • Lyz1
  • Paneth cell
  • heterogeneity
  • lysozyme

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