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Innate lymphoid cells (ILCs) are abundant in mucosal tissues and involved in tissue homeostasis and barrier function. Although several ILC subsets have been identified, it is unknown if additional heterogeneity exists, and their differentiation pathways remain largely unclear. We applied mass cytometry to analyze ILCs in the human fetal intestine and distinguished 34 distinct clusters through a t-SNE-based analysis. A lineage (Lin) - CD7 + CD127 - CD45RO + CD56 + population clustered between the CD127 + ILC and natural killer (NK) cell subsets, and expressed diverse levels of Eomes, T-bet, GATA3, and RORγt. By visualizing the dynamics of the t-SNE computation, we identified smooth phenotypic transitions from cells within the Lin - CD7 + CD127 - CD45RO + CD56 + cluster to both the NK cells and CD127 + ILCs, revealing potential differentiation trajectories. In functional differentiation assays, the Lin - CD7 + CD127 - CD45RO + CD56 + CD8a - cells could develop into CD45RA + NK cells and CD127 + RORγt + ILC3-like cells. Thus, we identified a previously unknown intermediate innate subset that can differentiate into ILC3 and NK cells., (© 2018 Li et al.)

Objective. Increased numbers of IL-17-producing CD4+ T cells have been observed in AS. However, it is not known whether these CD4+ T cells are already present in early disease or if this is a late disease phenomenon only. Therefore we aimed to investigate whether IL-17-producing CD4+ T cells are involved in early active axial SpA, including patients without imaging abnormalities, by determining the frequency and phenotype of IL-17-producing CD4+ T cells in these patients. Methods. Flow cytometry was used to analyse cytokine production and surface marker expression of peripheral blood mononuclear cells from 31 patients suffering from early active HLA-B27-positive axial SpA fulfilling the Assessment of SpondyloArthritis International Society criteria with or without MRI abnormalities and 21 healthy controls. Results. Patients with early active axial SpA showed an increased percentage of IL-17-producing CD4+ T cells compared with healthy controls (mean 1.1% vs 0.4%, respectively; P = 0.013). The percentage of IL-17-producing CD4+ T cells was equally increased in patients with and without MRI abnormalities (1.2% vs 1.1%, respectively; P = 0.81). These IL-17-producing CD4+T cells expressed the αβT cell receptor but not the γδ T cell receptor, exhibited a memory phenotype and expressed CD161, but only sporadically expressed killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2). Conclusion. IL-17-producing CD4+ T cells are increased in patients with early active axial SpA both with and without MRI abnormalities. This finding shows that the frequency of IL-17-producing CD4+ T cells is enhanced in the early stages of disease. [ABSTRACT FROM AUTHOR]

Objective Refractory coeliac disease type II (RCDII) is a severe complication of coeliac disease (CD) characterised by aberrant intraepithelial lymphocytes (IELs) of unknown origin that display an atypical CD3-CD7+icCD3+ phenotype. In approximately 40% of patients with RCDII these lymphocytes develop into an invasive lymphoma. In the current study we aimed to identify the physiological counterpart of these cells. Design RCDII cell lines were compared with T-cell receptor positive (TCR+) IEL (T-IEL) lines by microarray analysis, real-time quantitative PCR and flow cytometry. This information was used to identify cells with an RCDIIassociated phenotype in duodenal biopsies from nonrefractory individuals by multicolour flow cytometry. Results RCDII lines were transcriptionally distinct from T-IEL lines and expressed higher levels of multiple natural killer (NK) cell receptors. In addition to the CD3-CD7+icCD3+ phenotype, the RCDII lines were distinguishable from other lymphocyte subsets by the absence of CD56, CD127 and CD34. Cells matching this surface lineage-negative (Lin-) CD7+CD127-CD34- phenotype expressed a functional interleukin-15 (IL-15) receptor and constituted a significant proportion of IELs in duodenal specimens of patients without CD, particularly children, and were also found in the thymus. In patients without CD, the Lin-CD7+CD127-CD34- subset was one of four subsets within the CD3-CD7+icCD3+ population that could be distinguished on the basis of differential expression of CD56 and/or CD127. Conclusion Our studies indicate that the CD3-CD7+icCD3+ population is heterogeneous and reveal the existence of a Lin- subset that is distinct from T, B, NK and lymphoid tissue inducer cells. We speculate that this IL-15 responsive population represents the physiological counterpart of aberrant cells expanded in RCDII and transformed in RCDII-associated lymphoma. [ABSTRACT FROM AUTHOR]