![]() ![]() This requirement holds true not only for ILCs, but for various immune cell subsets, as tissue-associated features generally define tissue and organ function and, thus, decide over health or disease. In line with these functional characteristics, their microanatomical localization within and across tissues should fulfill particular needs and, therefore, histological approaches are needed to further understand ILC biology in context, as recent reports have pointed out 12, 13. Helper ILCs are mainly known to be tissue-resident cells 8, to be particularly abundant in barrier sites, and to act as sensors for tissue integrity, both promoting inflammation or tissue regeneration and wound healing 1, 9, 10, 11. Consequently, at least eight markers are needed to unambiguously identify these cells and several more are desired, in order to properly characterize their phenotype. This lineage marker combination is particularly used in humans, with some variations for analyses in mice. While NK cells are CD127 -/lo, expression of CD127 is a hallmark of all helper ILCs, which are commonly defined as CD45 +CD127 + lymphocytes that lack expression of other lineage (Lin) markers, such as CD3, CD19, CD14, CD123, CD141, and FcεRIα 2. ![]() ILCs are nowadays dissected into cytotoxic ILCs, namely NK cells, and helper ILCs, which are further classified into ILC1, ILC2, and ILC3. ![]() These added valuable and previously unappreciated information on ILC functional classification, activation states, and developmental trajectories. ![]() Since their discovery, ILCs have been extensively studied in several mice and human tissues by flow cytometry and, more recently, by single-cell approaches based on RNA sequencing 3, 4, 5 and mass cytometry 6, 7. ILCs were described as the innate counterparts of T cells because although lacking antigen-specific receptors, they share lineage-defining transcription factors (TF), chemokine receptors, and cytokine profiles with T lymphocytes 2. Innate lymphoid cells (ILCs) constitute a heterogeneous and rare cell population of lymphocytes identified only about a decade ago 1. ![]()
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