Alternative activation generates IL-10 producing type 2 innate lymphoid cells

Abstract

Type 2 innate lymphoid cells (ILC2) share cytokine and transcription factor expression with CD4+ Th2 cells, but functional diversity of the ILC2 lineage has yet to be fully explored. Here, we show induction of a molecularly distinct subset of activated lung ILC2, termed ILC210. These cells produce IL-10 and downregulate some pro-inflammatory genes. Signals that generate ILC210 are distinct from those that induce IL-13 production, and gene expression data indicate that an alternative activation pathway leads to the generation of ILC210. In vivo, IL-2 enhances ILC210 generation and is associated with decreased eosinophil recruitment to the lung. Unlike most activated ILC2, the ILC210 population contracts after cessation of stimulation in vivo, with maintenance of a subset that can be recalled by restimulation, analogous to T-cell effector cell and memory cell generation. These data demonstrate the generation of a previously unappreciated IL-10 producing ILC2 effector cell population.

The group 2 innate lymphoid cell (ILC2) regulatory network and its underlying mechanisms

“…In vitro, IL‐2 induces IL‐9 production from lung ILC2s although “activating cytokines” alone do not induce IL‐9 production . Furthermore, a recent study shows that a combination of IL‐2+ IL‐33 is capable of inducing IL‐10 production from ILC2s without expression of FOXP3, the transcription factor related to regulatory T cells . Therefore, IL‐2 has a function to enhance cell survival and modify the cytokine production from ILC2s.…”

Innate lymphoid cells, mediators of tissue homeostasis, adaptation and disease tolerance

“…Analogous to their regulatory T lymphocyte counterparts, they play an important role in preventing inflammation in the intestine . It is an ongoing debate if ILCreg are an independent ILC lineage or rather a functional state of ILC1‐3, characterized by IL‐10 expression . We refer to other articles in this issue for an in‐depth description of the various ILC groups and will only briefly summarize the major pillars here.…”

New insights into the function, development, and plasticity of type 2 innate lymphoid cells

“…These IL‐10‐producing CD45 + CD127 + Sca‐1 + cells were elevated in the axillary, inguinal lymph node, and ear tissue. Another study demonstrated in vitro the capability of mouse ILC2s to produce massive amounts of IL‐10 in response to IL‐33 plus retinoic acid stimulation and the downregulation of pro‐inflammatory genes . Wang et al found a subset of IL‐10‐producing ILCs in the human and mouse lamina propria of the small intestine, small intestinal epithelium, and colon lamina propria.…”