Circulating ILC precursors expressing CD62L exhibit a type 2 signature distinctly decreased in psoriatic patients

Human CD117⁺ CRTH2^neg innate lymphoid cells (ILC) comprise multipotent precursors (ILCp), which are able to differentiate into subtypes in response to different signals received in peripheral tissues. NKp46⁺ ILCp have been reported to associate with ILC3 whereas KLRG1⁺ ILCp with ILC2, although the latter can also generate other ILC subsets, thus, maintaining a substantial plasticity. We here showed that CD62L is expressed by ILCp exclusively within KLRG1⁺ population and its expression marks a loss of their broad differentiation potential. Analysis of cytokine production and relevant markers demonstrated that CD62L⁺ ILCp mainly differentiate into ILC2 whereas CD62L^neg counterpart can also differentiate into other ILC subsets depending on the signals they receive. Remarkably, in peripheral blood of psoriatic patients, where ILC3 are usually enriched, CD62L⁺ ILC were drastically reduced, whereas CD62L^neg ILC2 upregulated both RORγt and NKp46, thus, suggesting an ongoing conversion to ILC3. Therefore, CD62L now emerges as a potential marker to identify a skewing toward type 2 among ILCp.