Metabolic Control of Innate Lymphoid Cell Migration

Abstract

Innate lymphoid cells (ILCs) are specialized immune cells that rapidly respond to environmental challenges, such as infection and tissue damage. ILCs play an important role in organ homeostasis, tissue repair, and host defense in the mucosal tissues intestine and lung. ILCs are sentinels of healthy tissue function, yet it is poorly understood how ILCs are recruited, strategically positioned, and maintained within tissues. Accordingly, ILC migration is an area that has recently come into focus and it is important to define the signals that control ILC migration to and within tissues. In this context, signals from the local tissue microenvironment are relevant. For example, ILCs in the intestine are exposed to an environment that is rich in dietary, microbial, and endogenous metabolites. It has been shown that the Vitamin A metabolite retinoic acid promotes ILC1 and ILC3 homing to the intestine. In addition, recent studies have discovered cholesterol metabolites (oxysterols) as a novel class of molecules that regulate ILC migration through the receptor GPR183. ILCs are considered to be largely tissue-resident cells, yet recent data indicate that ILCs actively migrate during inflammation. Furthermore, the discovery of circulating ILC precursors in humans and their presence within tissues has fueled the concept of local ILC-poiesis. However, it is unclear how circulating ILCs enter tissue during embryogenesis and inflammation and how they are directed to local tissue niches. In this review, I will discuss the metabolic signals that regulate ILC homing and their strategic positioning in healthy and inflamed tissues. It is becoming increasingly clear that ILC function is closely linked to their tissue localization. Therefore, understanding the tissue signals that control ILC migration could open new avenues for the treatment of chronic inflammatory diseases and cancer.

Taurine Metabolism Aggravates the Progression of Lupus by Promoting the Function of Plasmacytoid Dendritic Cells

“…The approximate concentration of metabolites reflecting the physiologic state is difficult to determine. The concentration of metabolites varies according to the microenvironment (43), and there is usually a great difference between intracellular and extracellular levels. Taurine is found in low levels in plasma and extracellular fluids (range 10-100 μM), but exhibits high intracellular concentrations, reaching up to 50 mM (44).…”

Pleiotropic Role and Bidirectional Immunomodulation of Innate Lymphoid Cells in Cancer

“…ILC3s are heterogeneous but consistently require transcription factor RORγt for their development and function. LTis are related to ILC3s with distinct functions in the secondary lymphoid organ formation during both embryonic and adult stages of development (8,11,20). In general, these cells found in adult mice are termed LTilike cells, which have a similar phenotype to LTis (21).…”

“…Regardless of the functional association with ILC3s, LTis are considered a separate ILC lineage. Fetal liver-derived LTiPs express α4β7 integrin and C-C Motif Chemokine Receptor 6 (CCR6), whereas adult LTis derived from bone marrow precursors display upregulated RORγt in a Notch-dependent manner (9,20). Adult mice also have T-bet-expressing CCR6 − NKp46 + ILC3s derived from CCR6 − NKp46 − ILC3s (23) (Figure 1).…”

A Pan-cancer analysis of GPR183 correlated with tumor immunity

“…GPR183 played vital role in cell communication, migration and development of lymphocytes [16,17]. Recently, some studies have found GPR183 mediated intestinal immunity and in ammation by inducing migration and development of Group 3 innate lymphoid cells(ILC3s) [18][19][20]. Though GPR183 has intimate connection to body immunity, its role in tumor immunity remains mysterious.…”