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 Ag. 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 group 1 ILC (ILC1) contains CD4+ CD82, CD42 CD8+, and CD42 CD82 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+ group 3 ILC, but not CD42 ILC1 or group 2 ILC, 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 CD42 ILC1 are functionally divergent based on their IL- 6Ra expression and that the frequency of IL-6Ra expression on ILC is altered in SSc. The distinct phenotypic and functional features of CD4+ and CD42 ILC1 suggest that they may have differing roles in the pathogenesis of immune-mediated diseases, such as SSc.
Bibliographical noteFunding Information:
We thank Thien-Son Nguyen and all members of the BRI clinical core who aided in subject recruitment and samples management; Vivian Gersuk and the BRI genomics and bioinformatics core staff who performed the library construction, sequencing, and data processing for the RNAseq; and Alyssa Sheih for critical review of the manuscript.
©2016 by The American Association of Immunologists, Inc.