Regulatory Innate Lymphoid Cell (ILCreg) Markers

Overview

Regulatory innate lymphoid cells (ILCregs) are a population of IL-10-secreting innate lymphoid cells (ILCs) present in both mouse and human intestines that was found to suppress ILC1- and ILC3-induced intestinal inflammation. ILCregs arise from a common helper-like innate lymphoid precursor (CHILP) cell that can also give rise to ILC1s, ILC2s, ILC3s, and LTi cells, but not from the PLZF⁺ common ILC precursor (ILCP) that gives rise to ILC1s, ILC2s, ILC3s, suggesting that ILCregs are a distinct cell lineage. Similar to regulatory T cells (Tregs), ILCregs constitutively express high levels of TGF-beta RI, TGF-beta RII, CD122/IL-2 R beta, and IL-2 R gamma/Common gamma chain. Accordingly, IL-2 and TGF-beta 1 were found to be required for the proliferation and/or maintenance of ILCregs. In both mouse and human, ILCregs are phenotypically identified as Lin^-CD45⁺CD127/IL-7 R alpha⁺IL-10⁺ cells that also express CD25/IL-2 R alpha, CD90/Thy1, and Sca-1/Ly6, and lack expression of markers associated with other ILC subsets including NK1.1 and NKp46 (ILC1s), ST2 and KLRG1 (ILC2s), and NKp46 and ROR gamma t (ILC3s). ILCregs were also found to uniquely express the transcriptional regulator, Id3, and secrete large amounts of TGF-beta 1 in addition to IL-10.