Innate Lymphoid Cell Dynamics in Immune Responses

Innate lymphoid cells (ILCs) constitute a family of tissue‐resident effectors that orchestrate rapid immune responses at barrier surfaces and within organs. Divided into three main subsets—ILC1, ILC2 and ILC3—these cells mirror T‐helper functionality without antigen specificity, responding to local alarmins and cytokines to secrete key mediators such as interferon-γ, interleukin-13 and interleukin-22. Their dynamic behaviour—including migration directed by chemokines, adhesion via integrins and intercellular crosstalk through Notch- and cytokine-driven pathways—shapes host defence against pathogens, regulates tissue repair and fibrosis, and influences tumour immunity. Dysregulation of ILC trafficking or effector functions contributes to chronic inflammation, autoimmunity and cancer progression. Understanding these dynamics offers routes to novel diagnostics and targeted therapies that harness or restrain ILC activities in diverse clinical settings.

Research from Nature Portfolio

Recent studies have revealed that ILC3s bearing natural cytotoxicity receptors accumulate at the edge of tumour‐associated lymphoid aggregates in early‐stage lung carcinoma, where they secrete interleukin-22, tumour necrosis factor and other cytokines to induce and stabilise tertiary lymphoid structures. This tissue‐inducing property correlates with improved local immune surveillance and patient prognosis. Complementary work in acute promyelocytic leukaemia describes a lipid-mediated immunosuppressive circuit: tumour‐derived prostaglandin D2 and B7H6 engage CRTH2 and NKp30 on ILC2s, driving interleukin-13‐dependent expansion of myeloid-derived suppressor cells. Interrupting this axis restores anti‐tumour T‐cell activity, illustrating how ILC subsets can both potentiate and impede effective immunity depending on microenvironmental cues.

Innate Lymphoid Cell Dynamics in Immune Responses publication trend

The graph below shows the total number of articles in innate lymphoid cell dynamics in immune responses across all publications each year (not limited to Nature Index journals).

Technical terms

Innate lymphoid cells (ILCs): Tissue‐resident lymphoid effectors lacking antigen receptors, rapidly releasing cytokines in response to local stress or infection.

ILC2 and ILC3: Subsets specialised in type 2 (e.g. IL-5, IL-13) and type 3 (e.g. IL-17, IL-22) cytokine responses, with distinct roles in allergy, mucosal defence and tissue repair.

Cytokine amphiregulin: A reparative growth factor secreted by ILC2s that promotes epithelial cell proliferation and barrier restoration.

Integrin α4β7: A heterodimeric adhesion receptor guiding lymphoid cell retention in inflamed tissues via binding to endothelial and matrix ligands.

Tertiary lymphoid structures (TLSs): Ectopic lymphoid aggregates forming in chronic inflammation or tumours, supporting local antigen presentation and adaptive responses.

Myeloid-derived suppressor cells (MDSCs): Immature myeloid progenitors that expand under pathological conditions to inhibit T‐cell activation and promote immune evasion.

Notch signalling: A cell‐to‐cell communication pathway whereby membrane-bound ligands engage Notch receptors, influencing cell differentiation and effector fate.

References

1. The protective roles of integrin α4β7 and Amphiregulin-expressing innate lymphoid cells in lupus nephritis. Cellular & Molecular Immunology (2024).
2. Deep immunophenotyping reveals that autoimmune and autoinflammatory disorders are spread along two immunological axes capturing disease inflammation levels and types. Annals of the Rheumatic Diseases (2024).
3. Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures. Advanced Science (2023).
4. NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures. Nature Communications (2015).
5. Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis. Nature Communications (2017).