Characterisation of innate lymphoid cell populations at different sites in mice with defective T cell immunity

Abstract

Innate lymphoid cells (ILCs) have now been identified within Background most tissues of the body and current evidence indicates that this family of cells play a fundamental role in maintaining tissue homeostasis. However, few studies have compared the ILC populations between several tissues.: We sought to generate a comprehensive characterisation of the ILC Methods populations in different tissues of C57BL/6 WT and genetically modified mice targeting costimulatory pathways, using transcription factor expression to define specific groups.: Consistent with studies individually describing the ILC composition in Results different tissues, our analysis revealed different ILC groups dominate the ILC population in different tissues. Additionally, we observed a population of IL-7Rα Id2 cells lacking expression of lineage markers but also lacking expression of GATA-3, RORgt or T-bet. This population was most evident in ear skin where it outnumbered the defined ILC groups, however, further experiments demonstrated that detection of these cells was influenced by how the tissue was digested, raising concerns as to its real nature. Since both ILC2 and ILC3 express ICOS, we then investigated the requirement for ICOS:ICOSL interactions in the homeostasis of ILC populations at these sites. Surprisingly, no significant differences were detected in the number of ILC1, ILC2 or ILC3 between WT and ICOSL mice in any tissue, indicating that this pathway is not required for ILC homeostasis at these sites. These data were compared with CD80 CD86 mice given evidence of CD28 expression by some ILC and ILC crosstalk with activated T cells. Notably, the absence of CD28 ligands resulted in a significant increase in ILC2 and ILC3 numbers in the intestine.: Together, these data provide new insight into ILC composition in Conclusions different tissues in both WT and genetically modified mice where key costimulatory pathways are genetically deleted, providing a useful resource for further research into ILC biology.

Intervention of oncostatin M-driven mucosal inflammation by berberine exerts therapeutic property in chronic ulcerative colitis

“…Single-cell suspensions from the colonic lamina propria were prepared as previously described 30,31 . Colon samples in each group were cut into small pieces and incubated in RPMI-1640 containing 10% FBS and 5 mM EDTA for 15 min and then digested using 0.5 mg/ml Type IV collagenase, 3 mg/ml dispase II, and 0.1 mg/ml DNase I in a 37°C shaking incubator for 30 min.…”

“…5c). The subsets of ILCs reflected functional categories of T helper subsets and transcriptional factors, T-bet, GATA3, and RORγT were adopted to identify ILC1, ILC2, and ILC3, respectively 31,40 . We found berberine showed ability to decrease the subpopulation of ILC1 (T-bet + ), ILC3 (RORγT + ), and the numbers of ILC2 (GATA3 + ) (Fig.…”

The Role of Innate Lymphoid Cells in the Regulation of Immune Homeostasis in Sepsis-Mediated Lung Inflammation

“…The pathological roles of aberrantly activated lung macrophages and infiltrating neutrophils in ALI are well documented [ 49 ]; however, the mechanism of sepsis-induced lung injury remains poorly understood. ILC2s, the predominant population of ILCs in the lung [ 7 ], have garnered attention as a new player regulating type 2 immune responses. IL-5 and IL-13, representative type 2 cytokines produced by ILC2, have been shown to protect against lung injury and sepsis [ 50 , 51 , 52 ].…”

“…ST2 (also known as IL1RL1) is a receptor of IL-33 and is also expressed on a variety of immune cells, such as Th2 cells [ 64 ], regulatory T cells [ 65 ], mast cells [ 66 ], M2 macrophages [ 67 ], and eosinophils [ 68 ]. ST2 serves as a marker of murine lung ILC2s [ 7 ]. The expression levels of ST2 on ILC2s differs based on where the latter is located [ 69 ].…”

“…This review focuses on recent advances in the understanding of the regulation and function of ILC2s in sepsis-induced lung inflammation; in particular, the balance between IL-33/ST2 and PD-L1/PD-1 signaling in ILC2s. ILC2s, the predominant subset population of ILCs in the lung [ 7 ], are characterized by secretion of the type 2 cytokines IL-5, IL-9, and IL-13. Recent studies have demonstrated that IL-33 activates ILC2s-mediated type 2 cytokines to prevent lung injury [ 8 ] and decreases the mortality of mice afflicted with Staphylococcus aureus bacteremia [ 9 ].…”