A Human Lin− CD123+ CD127low Population Endowed with ILC Features and Migratory Capabilities Contributes to Immunopathological Hallmarks of Psoriasis

Abstract

Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127− ILC populations and an early ILC precursor (EILP) CD127low. ILC development has predominately been investigated in mouse models. However, in humans, different transcription factors have been described for ILC identification. NFIL3 (nuclear factor, IL-3 regulated) is crucial for ILC development in response to IL-7. CD123 (IL-3Rα) is usually used to exclude basophils during ILC identification, however, it is unknown if in response to IL-3, NFIL3 could be relevant to induce ILC features in Lin− CD123+ populations in addition, is also unknown whether peripheral blood (PB) population with ILC features may have skin-homing potential to participate in skin inflammatory chronic diseases. Here, we report a Lin− CD123+ CD127low CD7+ CLA+ population that share some phenotypic properties with basophils, but expresses several transcription factors for ILC commitment such as inhibitor of DNA binding 2 (Id2), NFIL3, promyelocytic leukemia zinc finger (PLZF), thymocyte selection-associated high-mobility group box protein (TOX), and T cell factor-1 (TCF-1). In addition, this population expresses different ILC markers: CD132, CD90, CD161, α4 integrin, c-Kit, CRTH2, AhR, and IL-23R. IL-3 prevents apoptosis and increases their NFIL3, TOX, and PLZF expression. In PB, the CD123+ CD127low population is predominantly a conspicuous population that expresses T-bet and RORγt. The Lin− CD123+ CD127low population in PB has a limited Th type cytokine expression and highly expresses IL-8. The Lin− CD123+ CD127low population expresses skin-homing receptors (cutaneous lymphocyte antigen and CXCR4) and transmigrates through endothelial cells in response to SDF-1. An equivalent Lin− CD123low population was identified in control skin, which shows a broader phenotypic diversity and cytokine production, including IL-22 and IL-17. Remarkably, the CD123low population in the lesion and non-lesion skin of psoriasis patients expresses IL-17 and IL-22. Our findings suggest the identification of an alternative Lin− CD123+ CD127low population with ILC features endowed with migratory capabilities that might contribute to immunopathological hallmarks of psoriasis.

Exposure of Intestinal Epithelial Cells to Short- and Long-Chain Fructo-Oligosaccharides and CpG Oligodeoxynucleotides Enhances Peanut-Specific T Helper 1 Polarization

“…CRTH2 is a prostaglandin D2 receptor, and is a surface marker that is selectively expressed on, for instance, Th2 cells, but also on other cells involved in allergy, such as basophils and eosinophils ( 35 , 36 ). This reduction in CRTH2 corresponded with a decrease in a recently described new subset, a Lin − CD123 + CD127 low population (Figure 7 G) which shares some markers with both basophils and ILCs ( 37 ).…”

Human innate lymphoid cells (ILCs): Toward a uniform immune‐phenotyping

“…Indeed, ILCs have been initially defined as lineage negative (Lin 2 ) CD127 1 cells, but some groups have recently identified nonclassical human ILCs CD127 dim and mouse ILCs CD127 2 (that are out of the focus of this review) (13)(14)(15)(16). Indeed, ILCs have been initially defined as lineage negative (Lin 2 ) CD127 1 cells, but some groups have recently identified nonclassical human ILCs CD127 dim and mouse ILCs CD127 2 (that are out of the focus of this review) (13)(14)(15)(16).…”

“…The first concern in the study of ILCs is represented by the fact that several groups have used distinct criteria and markers for their identification. Indeed, ILCs have been initially defined as lineage negative (Lin 2 ) CD127 1 cells, but some groups have recently identified nonclassical human ILCs CD127 dim and mouse ILCs CD127 2 (that are out of the focus of this review) (13)(14)(15)(16). Moreover, it is difficult to determine what "Lineage" means for the different research teams.…”

Deciphering the evolution of vertebrate immune cell types with single-cell RNA-seq

“…Once a large number of such markers are available, new populations can be discovered by exploring T cell subsets expressing different combinations of them (e.g. Lin-CD123+ CD127low innate lymphoid cells (Mora-Velandia et al, 2017)). This approach has proved very powerful in mouse and human and resulted in a detailed phenotypic and functional characterization of immune cell populations in these two species.…”