Innate Lymphoid Cells: ILC1, ILC2 & ILC3
An innate lymphoid cell is a T-helper cell with the antigen receptor removed and nothing else changed. The same three master transcription factors \u2014 T-bet, GATA3, ROR\u03b3t \u2014 running the same three cytokine programmes, in a cell that cannot see antigen at all. What replaces the receptor is the epithelium: IL-33, TSLP, IL-25, IL-12, IL-18 and IL-23 arrive from damaged or infected barrier tissue and choose the response before any antigen-specific cell has seen anything. That is the whole point of the family \u2014 they are fast because they are already differentiated, and they sit in tissue rather than circulating. It is also why so many phenotypes assigned to T cells turn out, on re-examination in a T-cell-deficient host, to belong here. Click any protein for the matching Assay Genie ELISA kit or In Vivo antibody.
Same transcription factors, no antigen receptor. This is the fact worth carrying away from the map. T-bet, GATA3 and ROR\u03b3t are not analogues of the Th1, Th2 and Th17 regulators \u2014 they are the same genes, doing the same jobs, in a cell that cannot recognise anything. Evolutionarily the ILC module came first and the T cell bolted a receptor onto it. Practically, it means the effector cytokine tells you nothing about which cell made it: IFN-\u03b3 from an ILC1 and IFN-\u03b3 from a Th1 are the same molecule. Any knockout or neutralisation experiment that assumes a cytokine is T-cell-derived is making an assumption the data rarely tests, and the correction \u2014 repeating it in a Rag-deficient host \u2014 has reassigned a long list of phenotypes to this family.
The epithelium chooses the response. With no receptor to engage, what selects between the three modules is the alarmin arriving from the barrier. IL-33 is stored pre-made in the nucleus of healthy epithelium and released on necrosis, so the signal is damage rather than infection; TSLP and IL-25 report different insults, with IL-25 coming specifically from tuft cells, the rare chemosensory epithelial cells that detect helminths. IL-12 with IL-18 selects type 1, IL-23 with IL-1\u03b2 selects type 3. One assay caution worth stating: soluble ST2 is a decoy receptor, so a rising serum sST2 means less IL-33 signalling reaching the cell, not more. It is among the most commonly misread analytes in this area.
Type 2 is a repair programme that also causes allergy. Amphiregulin is the node that reframes ILC2: it restores epithelial integrity after influenza, and the same cell in the same state drives the goblet-cell metaplasia and smooth-muscle contraction of asthma through IL-13. IL-5 is constitutive rather than induced in tissue ILC2, which is why baseline eosinophil counts track ILC2 activity and why anti-IL-5 antibodies work on a cell type that is not an eosinophil. IL-9 is autocrine, so a transient alarmin becomes a self-sustaining response \u2014 a good mechanistic reason why blocking the alarmin late so often disappoints. The type 3 module carries the mirror-image problem: IL-22 acts only on epithelium and is purely protective, IL-17A comes from the same cell and is inflammatory, and blocking IL-17 in inflammatory bowel disease removed the protection along with the pathology.
The In Vivo tie-in, and it is unusually direct. 12 of the 37 nodes carry a functional-grade antibody, and two of them \u2014 CD127 and Thy-1 \u2014 are not merely targets on this pathway but the standard tools for studying it. Anti-Thy-1 in a T-cell-deficient host is the experiment that assigned function to ILCs in the first place, and lineage-negative CD127-positive is how every ILC in every paper is gated. Also blockable: NK1.1, CD25, IL-2, IL-1\u03b2, IL-4, IFN-\u03b3, TNF, GM-CSF, IL-10 and pan-TGF-\u03b2. Stated plainly, what is not: there is no functional-grade anti-IL-33, anti-ST2, anti-TSLP, anti-IL-25, anti-IL-5, anti-IL-13, anti-IL-17A, anti-IL-22 or anti-IL-23 in this range. The alarmins that start the pathway and the type 2 and type 3 cytokines that finish it are measurable, not blockable. The workable design is therefore to delete the cell and measure the cytokine, rather than to neutralise the cytokine and infer the cell. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — ELISA kit, In Vivo antibody or research antibody.