CD4+ Group 1 Innate Lymphoid Cells (ILC) Form a Functionally Distinct ILC Subset That Is Increased in Systemic Sclerosis

Abstract

Innate lymphoid cells (ILC) are a heterogeneous group of cellular subsets that produce large amounts of T cell-associated cytokines in response to innate stimulation in the absence of antigen. In this study, we define distinct patterns of surface marker and cytokine expression among the ILC subsets that may further delineate their migration and function. Most notably, we found that the subset previously defined as ILC1 contains CD4+ CD8−, CD4− CD8+ and CD4− CD8− populations. Although all ILC1 subsets shared characteristics with Th1 cells, CD4+ ILC1 also demonstrated significant phenotypic and functional heterogeneity. We also show that the frequencies of CD4+ ILC1 and NKp44+ ILC3, but not CD4− ILC1 or ILC2, are increased in the peripheral blood of individuals with systemic sclerosis (SSc), a disease characterized by fibrotic and vascular pathology as well as immune dysregulation. Furthermore, we demonstrate that CD4+ and CD4− ILC1 are functionally divergent based on their IL-6Rα expression, and that the frequency of IL-6Rα expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4+ and CD4− ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases such as systemic sclerosis.

ILC2-modulated T cell–to-MDSC balance is associated with bladder cancer recurrence

“…It was recently reported that ILC2 expressed the chemokine receptor CCR4 and did so at higher proportions than was observed with ILC1 or ILC3 (21). We confirmed that CCR4 was expressed on peripheral ILC2 from patients with NMIBC, and at a significantly higher frequency than was observed on ILC1 or ILC3 (Supplemental Figure 6A).…”

NK cells and type 1 innate lymphoid cells: partners in host defense

“…CD127 + CRTH2 − CD117 − ILCs express cytoplasmic CD3 and a number of other T cell markers including CD4, CD8, CD27 and CD28, but do not express αβ TCR or γδ TCR in the cytoplasm and no CD3-TCR complex on the cell surface 43 . Because these cells express T-bet and the chemokine receptor CXCR3 (which are also expressed on T H 1 cells) but lack Eomes, they were considered to be ILC1s.…”

Human ILC1: To Be or Not to Be

“…For example, two groups have reported that human peripheral-blood ILC1s are defined by the absence of cell-surface CD3, TCRαβ, and TCRγδ but express CD5 (Roan et al., 2016), a finding that has been confirmed by single-cell RNA-sequencing analysis of tonsillar ILC1s (Björklund et al., 2016) and in our lab by flow cytometry. Furthermore, ILC1s can be cloned under T-cell-promoting conditions without developing into T cells.…”