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

Authors

Iyshwarya Balasubramanian, Federated Department of Biological Sciences
Sheila Bandyopadhyay, Federated Department of Biological Sciences
Juan Flores, Federated Department of Biological Sciences
Jared Bianchi-Smak, Federated Department of Biological Sciences
Xiang Lin, Department of Computer Science
Haoran Liu, Department of Computer Science
Shengxiang Sun, Washington University School of Medicine in St. Louis
Natasha B. Golovchenko, Center for Immunity and Inflammation
Yue Liu, Federated Department of Biological Sciences
Dahui Wang, Federated Department of Biological Sciences
Radha Patel, Federated Department of Biological Sciences
Ivor Joseph, Federated Department of Biological Sciences
Panan Suntornsaratoon, Rutgers New Jersey Medical School
Justin Vargas, Columbia University Irving Medical Center
Peter H.R. Green, Columbia University Irving Medical Center
Govind Bhagat, Columbia University Irving Medical Center
Stephen M. Lagana, Columbia University Irving Medical Center
Wang Ying, Hackensack Meridian Health

Document Type

Article

Publication Date

11-2-2023

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.

Identifier

85171281422 (Scopus)

Publication Title

EMBO Journal

External Full Text Location

https://doi.org/10.15252/embj.2023113975

e-ISSN

14602075

ISSN

02614189

PubMed ID

37718683

Issue

21

Volume

42

Grant

IOS‐1754783

Fund Ref

Directorate for Biological Sciences

Recommended Citation

Balasubramanian, Iyshwarya; Bandyopadhyay, Sheila; Flores, Juan; Bianchi-Smak, Jared; Lin, Xiang; Liu, Haoran; Sun, Shengxiang; Golovchenko, Natasha B.; Liu, Yue; Wang, Dahui; Patel, Radha; Joseph, Ivor; Suntornsaratoon, Panan; Vargas, Justin; Green, Peter H.R.; Bhagat, Govind; Lagana, Stephen M.; and Ying, Wang, "Infection and inflammation stimulate expansion of a CD74+ Paneth cell subset to regulate disease progression" (2023). Faculty Publications. 1333.
https://digitalcommons.njit.edu/fac_pubs/1333