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Updated: Mar 16, 2026

Visualization of IL-22-expressing Lymphocytes Using Reporter Mice
Published on: January 25, 2017
Cell type-specific enhancers regulate IL-22 expression in innate and adaptive type 3 lymphoid cells
Ankita Saini1,2, Leone S Hopkins1, Vanida A Serna1
1Department of Microbial Infection and Immunity, The Ohio State University, Columbus, OH, USA.
Researchers identified two key DNA enhancers, E22-1 and E22-2, that control Interleukin-22 (IL-22) expression in immune cells. These enhancers are crucial for fighting infections and preventing inflammatory diseases like psoriasis.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Interleukin-22 (IL-22) is vital for epithelial barrier immunity and host defense.
- Dysregulated IL-22 contributes to chronic inflammatory conditions.
- Transcriptional regulation of IL-22 expression is not fully understood.
Purpose of the Study:
- To identify and characterize novel regulatory elements controlling Il22 gene expression.
- To investigate the distinct roles of these elements in different type 3 lymphoid cell subsets.
- To understand the molecular mechanisms underlying IL-22 regulation in immunity and disease.
Main Methods:
- Identification and functional analysis of putative enhancers (E22-1, E22-2) using genetic and molecular techniques.
- Assessment of enhancer activity in T helper 17/22 (Th17/22) and type 3 innate lymphoid cells (ILC3).
- In vivo studies using mouse models of infection (Citrobacter rodentium) and inflammation (psoriasis).
Main Results:
- Two novel enhancers, E22-1 and E22-2, were identified, exhibiting distinct regulatory capacities for Il22.
- Both enhancers are essential for protection against Citrobacter rodentium infection and IL-22-driven psoriasis.
- E22-2 specifically regulates IL-22 in ILC3s, dependent on Runx3 binding sites and lacking a RORγt motif.
- E22-1 regulates IL-22 in both Th17/22 and ILC3 cells.
Conclusions:
- Type 3 lymphoid cells utilize distinct cis-regulatory elements (enhancers) to modulate IL-22 expression.
- Differential regulation of IL-22 by E22-1 and E22-2 contributes to homeostatic immunity and pathogen defense at barrier tissues.
- Understanding these regulatory mechanisms offers potential therapeutic targets for IL-22-mediated inflammatory diseases.
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