Project description:The perinatal period is a critical window for the distribution of innate tissue-resident immune cells to developing organs. Despite epidemiologic evidence implicating early life environment in risk for allergy, temporally controlled lineage-tracing of ILC2s during this period has not been done. Using complementary fate-mapping approaches and fluorescent reporters of ILC2 activation, we demonstrate that ILC2s appear in multiple organs during late gestation similar to tissue macrophages, but unlike the latter, a majority of peripheral ILC2 pools are generated de novo during a postnatal window. This period was accompanied by systemic ILC2 priming and acquisition of tissue-specific expression profiles. Although perinatal ILC2s are variably replaced with age, the dramatic increases in tissue ILC2s following helminth infection are mediated through local expansion independent of de novo generation by BM hematopoiesis. We provide the first comprehensive temporally controlled fate-mapping of an innate lymphocyte subset with notable nuances as compared to tissue macrophage ontogeny
Project description:The perinatal period is a critical window for distribution of innate tissue-resident immune cells within developing organs. Despite epidemiologic evidence implicating the early-life environment in the risk for allergy, temporally controlled lineage tracing of group 2 innate lymphoid cells (ILC2s) during this period remains unstudied. Using complementary fate-mapping approaches and reporters for ILC2 activation, we show that ILC2s appeared in multiple organs during late gestation like tissue macrophages, but, unlike the latter, a majority of peripheral ILC2 pools were generated de novo during the postnatal window. This period was accompanied by systemic ILC2 priming and acquisition of tissue-specific transcriptomes. Although perinatal ILC2s were variably replaced across tissues with age, the dramatic increases in tissue ILC2s following helminth infection were mediated through local expansion independent of de novo generation by bone marrow hematopoiesis. We provide comprehensive temporally controlled fate mapping of an innate lymphocyte subset with notable nuances as compared to tissue macrophage ontogeny.
Project description:Group 2 innate lymphoid cells (ILC2s) in the lung are stimulated by inhaled allergens. ILC2s do not directly recognize allergens but they are stimulated by cytokines including interleukin (IL)-33 released by damaged epithelium.Lung ILC2s, upon stimulation, produce T helper 2 cell-type cytokines inducing T cell independent allergic lung inflammation. We now report that lung ILC2s, upon activation by an allergen or IL-33, acquire the properties of memory cells. The activated ILC2s initially proliferate and secrete cytokines, followed by a contraction phase as they stop producing cytokines. Nevertheless, some persist long after the resolution of the inflammation and acquire intrinsic capacities to react to unrelated allergens more vigorously than naïve ILC2s, thus mediating a severe allergic lung inflammation. Gene expression profiles of the previously activated ILC2s show a gene signature of memory T cells. These antigen non-specific memory ILC2s may explain why asthma patients are often sensitized to multiple allergens. ILC2s were isolated from mouse lungs from naive and IL-33 injected mice 4 days, 14 days and 4 months after the initial treatment. RNA was extracted from those ILC2 populations and analyzed for gene expression profiles. RNA was also extracted from ILC2s isolated from lung draining mediastinal lymph node (mLN) 4 days and 14 days after IL-33 treatment.
Project description:We analyzed the total proteome of group 2 innate lymphoid cells (ILC2s) after different stimulation with interleukin-33 (IL-33), a cytokine playing a critical role in human asthma, and TL1A, a TNF-family cytokine also known to activate ILC2s. Upon combined stimulation with IL-33 plus TL1A, we show that lung ILC2s produce high amounts of IL-9 and acquire a transient ‘ILC9’ phenotype. This phenotype is characterized by simultaneous production of large amounts of type 2 cytokines (IL-5, IL-13 and IL-9), induction of the IL-2 receptor CD25 (Il2ra), and of the transcription factors IRF4, JunB and BATF, that form immune-specific complexes known to induce IL-9 expression.
Project description:LTi cells are part of the ILC family and essential for the formation of secondary lymph nodes within the embryo. This data set contains the analysis of lymphoid tissue (LTi) cell ontogeny, studied by expression profile analysis with RNA bulk sequencing of the populations associated with LTi ontogeny isolated from fetal liver vs. embryonic periphery at embryonic stage E13.5. They indicate a proliferating precursor population mainly in the fetal liver, while the embryonic periphery harbors the definitive lineage.
Project description:The period of development from the last two weeks of gestation through the first two weeks of life spans a period of great functional and metabolic challenge to the fetal and neonatal lamb heart. Important changes in gene expression occur to meet these challenges. On this study, septa from sheep hearts at 130 days gestation (n=6), term (n=8, gestational lenght is around 145 days) and 14-days-old lambs (n=8) were used to model the changes in gene expression patterns during the perinatal period using Agilent 15k ovine microarrays. Weighted gene co-expression network analysis (WGCNA) determined five major patterns of co-expressed and functionally related genes during this critical period of cardiac transition. Septum samples from the heart were collected from non-treated fetuses at 130 days of gestational age (GA130d, n=6) and term (n=8); and from naturally born 14-days-old lambs (Lamb, n=8). None of the ewes suffered gestational diseases or showed signs of impending labor.
Project description:Transcriptomal comparison between group 2 innate lymphoid cells (ILC2s) in the murine small intestine (SI-ILC2s) and those in white adipose tissue (WAT-ILC2s).