Aging is accompanied by homeostatic and functional dysregulation of multiple immune cell subsets. Group 3 innate lymphoid cells (ILC3s) constitute a heterogeneous cell population that plays pivotal roles in intestinal immunity. In this study, we found that ILC3s in aged mice exhibited dysregulated homeostasis and function, leading to bacterial and fungal infection susceptibility. Moreover, our data revealed that the enrichment of the H3K4me3 modification in effector genes of aged gut CCR6 + ILC3s was specifically decreased compared to young mice counterparts. Disruption of Cxxc finger protein 1 (Cxxc1) activity, a key subunit of H3K4 methyltransferase, in ILC3s led to similar aging-related phenotypes. An integrated analysis revealed Kruppel-like factor 4 (Klf4) as a potential Cxxc1 target. Klf4 overexpression partially restored the differentiation and functional defects seen in both aged and Cxxc1-deficient intestinal CCR6 + ILC3s. Therefore, these data suggest that targeting intestinal ILC3s may provide strategies to protect against age-related infections.
Keyphrases
- nk cells
- induced apoptosis
- single cell
- cell cycle arrest
- regulatory t cells
- dendritic cells
- electronic health record
- big data
- high fat diet induced
- cell proliferation
- stem cells
- protein protein
- immune response
- type diabetes
- risk assessment
- machine learning
- adipose tissue
- middle aged
- signaling pathway
- skeletal muscle
- artificial intelligence
- bone marrow
- pi k akt