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Innate lymphoid cells

Etienne Becht, Yannick Simoni, Elaine Coustan-Smith, Evrard Maximilien, Yang Cheng, Lai Guan Ng, Dario Campana, Evan Newell
Motivation: Recent flow and mass cytometers generate datasets of dimensions 20 to 40 and a million single cells. From these, many tools facilitate the discovery of new cell populations associated with diseases or physiology. These new cell populations require the identification of new gating strategies, but gating strategies become exponentially more difficult to optimize when dimensionality increases. To facilitate this step, we developed Hypergate, an algorithm which given a cell population of interest identifies a gating strategy optimized for high yield and purity...
June 21, 2018: Bioinformatics
Thibaut Perchet, Maxime Petit, Elena-Gaia Banchi, Sylvain Meunier, Ana Cumano, Rachel Golub
The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC). We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade...
2018: Frontiers in Immunology
J L Brown, L Campbell, J Malcolm, A Adrados Planell, J P Butcher, S Culshaw
Innate lymphoid cells (ILCs) are a population of lymphocytes that act as the first line of immunologic defense at mucosal surfaces. The ILC family in the skin, lungs, and gastrointestinal tissues has been investigated, and there are reports of individual subsets of ILCs in the oral tissues. We sought to investigate the whole ILC population (group 1, 2, and 3 subsets) in the murine gingivae and the lymph nodes draining the oral cavity. We show that ILCs made up a greater proportion of the whole CD45+ lymphocyte population in the murine gingivae (0...
June 1, 2018: Journal of Dental Research
Marco Colonna
Type 1, 2, and 3 innate lymphoid cells (ILCs) have emerged as tissue-resident innate correlates of T helper 1 (Th1), Th2, and Th17 cells. Recent studies suggest that ILCs are more diverse than originally proposed; this might reflect truly distinct lineages or adaptation of ILCs to disparate tissue microenvironments, known as plasticity. Given that ILCs strikingly resemble T cells, are they redundant? While the regulation, timing, and magnitude of ILC and primary T cell responses differ, tissue-resident memory T cells may render ILCs redundant during secondary responses...
June 19, 2018: Immunity
Dylan E Cherrier, Nicolas Serafini, James P Di Santo
Innate lymphoid cells (ILCs) and natural killer (NK) cells have garnered considerable interest due to their unique functional properties in immune defense and tissue homeostasis. Our current understanding of how these cells develop has been greatly facilitated by knowledge of T cell biology. Models of T cell differentiation provided the basis for a conceptual classification of these innate effectors and inspired a scheme of their activation and regulation. In this review, we discuss NK cell and ILC development from a "T cell standpoint" in an attempt to extend the analogy between adaptive T cells and their innate ILC and NK cell counterparts...
June 19, 2018: Immunity
Maya E Kotas, Richard M Locksley
Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4+ T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense...
June 19, 2018: Immunity
Marina Babic, Chiara Romagnani
Accumulating evidence supports a role for the innate lymphoid cells (ILCs) in the modulation of T cell responses. In this issue of Immunity, Halim et al. (2018) identify a role for the costimulatory OX40-OX40L axis in ILC2-mediated regulation of adaptive type 2 immunity during helminth infection and allergen exposure.
June 19, 2018: Immunity
Kyoung-Jin Chung, Marina Nati, Triantafyllos Chavakis, Antonios Chatzigeorgiou
Immune cells are present in the adipose tissue (AT) and regulate its function. Under lean conditions, immune cells predominantly of type 2 immunity, including eosinophils, M2-like anti-inflammatory macrophages and innate lymphoid cells 2, contribute to the maintenance of metabolic homeostasis within the AT. In the course of obesity, pro-inflammatory immune cells, such as M1-like macrophages, prevail in the AT. Inflammation in the obese AT is associated with the development of metabolic complications such as insulin resistance, type 2 diabetes and cardiovascular disease...
June 19, 2018: Reviews in Endocrine & Metabolic Disorders
Annika Reinhardt, Immo Prinz
γδ T cells, αβ T cells, and innate lymphoid cells (ILCs) are capable of producing interleukin (IL)-17A, IL-17F, and IL-22. Among these three families of lymphocytes, it is emerging that γδ T cells are, at least in rodents, the main source of these key pro-inflammatory cytokines. γδ T cells were implicated in multiple inflammatory and autoimmune diseases, including psoriasis, experimental autoimmune encephalomyelitis and uveitis, colitis, and rheumatoid arthritis. Recent findings pointed toward a central role of γδ T cells in the pathogenesis of spondyloarthritis (SpA), a group of inflammatory rheumatic diseases affecting the axial skeleton...
2018: Frontiers in Immunology
Naomi Tsurikisawa, Chiyako Oshikata, Maiko Watanabe, Takahiro Tsuburai, Takeshi Kaneko, Hiroshi Saito
BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a disease characterized by allergic granulomatosis, necrotizing vasculitis, and peripheral blood eosinophilia. Interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and type-2 innate lymphoid cells (ILC2) are involved in the innate and type-2 immune responses in EGPA. However, the relationships among these molecules and the mechanisms underlying the development of EGPA remain unknown. OBJECTIVE: We investigated the relationships among peripheral blood eosinophil count, serum IL-33 and TSLP concentration, and peripheral blood ILC2 count in patients with EGPA, chronic eosinophilic pneumonia (CEP), or bronchial asthma (BA)...
June 16, 2018: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Timotheus Y F Halim, Batika M J Rana, Jennifer A Walker, Bernhard Kerscher, Martin D Knolle, Helen E Jolin, Eva M Serrao, Liora Haim-Vilmovsky, Sarah A Teichmann, Hans-Reimer Rodewald, Marina Botto, Timothy J Vyse, Padraic G Fallon, Zhi Li, David R Withers, Andrew N J McKenzie
The local regulation of type 2 immunity relies on dialog between the epithelium and the innate and adaptive immune cells. Here we found that alarmin-induced expression of the co-stimulatory molecule OX40L on group 2 innate lymphoid cells (ILC2s) provided tissue-restricted T cell co-stimulation that was indispensable for Th2 and regulatory T (Treg) cell responses in the lung and adipose tissue. Interleukin (IL)-33 administration resulted in organ-specific surface expression of OX40L on ILC2s and the concomitant expansion of Th2 and Treg cells, which was abolished upon deletion of OX40L on ILC2s (Il7raCre/+ Tnfsf4fl/fl mice)...
May 31, 2018: Immunity
Beom K Choi, Sun H Hwang, Yu I Kim, Rohit Singh, Byoung S Kwon
The Hyaluronic Acid-rich Node and Duct System (HAR-NDS or NDS), Primo Vascular System (PVS) or Bonghan System (BHS), is thought to be a third circulatory system independent of the blood and lymphatic systems and a structure of connected nodes and ducts. Although it seems to be part of the immune system as it is enriched with cells of innate immunity, little is known about its immunological roles. We performed cellular profiling and secretome analysis of NDS in a steady state and under TLR2- or TLR4-mediated local inflammation, and found that the NDS is pre-dominantly enriched with the myeloid cells, selectively attracts the inflammatory macrophages and neutrophils, has a flexible structure just like the lymph node, and is structured with the fibroblastic reticular cells and reticular network...
June 12, 2018: Cytokine
Colleen M Lau, Joseph C Sun
Immunological memory is broadly understood as the underlying mechanism by which an organism remembers previous encounters with pathogens, aberrant cells, or self-antigens to produce a more rapid or robust secondary response upon re-encounter. This phenomenon is widely accepted as the hallmark feature of the adaptive immune system. However, work within the last decade has continuously challenged this viewpoint and opened up the idea that immunological memory extends beyond just conventional B cells and T cells...
June 11, 2018: Current Opinion in Immunology
Timothy N Perkins, Elizabeth A Oczypok, Pavle S Milutinovic, Regina E Dutz, Tim D Oury
BACKGROUND: The receptor for advanced glycation endproducts (RAGE) has been implicated as a critical molecule in the pathogenesis of experimental asthma/allergic airway inflammation (AAI). It has been previously shown that RAGE acts both upstream of interleukin-33 (IL-33) release and downstream of IL-33 release via RAGE-dependent IL-33 induced accumulation of type 2 innate lymphoid cells (ILC2s) in the lungs, which perpetuate type 2 inflammation and mucus metaplasia. However, the mechanism by which RAGE mediates downstream IL-33 induced type 2 inflammatory responses is unknown...
June 14, 2018: Allergy
Felipe Gálvez-Cancino, Ernesto López, Evelyn Menares, Ximena Díaz, Camila Flores, Pablo Cáceres, Sofía Hidalgo, Ornella Chovar, Marcela Alcántara-Hernández, Vincenzo Borgna, Manuel Varas-Godoy, Flavio Salazar-Onfray, Juliana Idoyaga, Alvaro Lladser
Memory CD8+ T cell responses have the potential to mediate long-lasting protection against cancers. Resident memory CD8+ T (Trm) cells stably reside in non-lymphoid tissues and mediate superior innate and adaptive immunity against pathogens. Emerging evidence indicates that Trm cells develop in human solid cancers and play a key role in controlling tumor growth. However, the specific contribution of Trm cells to anti-tumor immunity is incompletely understood. Moreover, clinically applicable vaccination strategies that efficiently establish Trm cell responses remain largely unexplored and are expected to strongly protect against tumors...
2018: Oncoimmunology
Kyu-Seon Oh, Rachel A Gottschalk, Nicolas W Lounsbury, Jing Sun, Michael G Dorrington, Songjoon Baek, Guangping Sun, Ze Wang, Kathleen S Krauss, Joshua D Milner, Bhaskar Dutta, Gordon L Hager, Myong-Hee Sung, Iain D C Fraser
Macrophage activation by bacterial LPS leads to induction of a complex inflammatory gene program dependent on numerous transcription factor families. The transcription factor Ikaros has been shown to play a critical role in lymphoid cell development and differentiation; however, its function in myeloid cells and innate immune responses is less appreciated. Using comprehensive genomic analysis of Ikaros-dependent transcription, DNA binding, and chromatin accessibility, we describe unexpected dual repressor and activator functions for Ikaros in the LPS response of murine macrophages...
June 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Yufei Xia, Jie Wu, Yiqun Du, Chunyu Miao, Zhiguo Su, Guanghui Ma
As peripheral lymphocytes are typically excluded from the gastrointestinal lymph tissues, current parenteral vaccinations fail to simultaneously induce systemic and mucosal responses. To break the natural barrier, "immunoticket" capsules are developed and heralded, which are designed with positive charged shells and oily core to spatiotemporally deliver antigens and all-trans retinoic acid (RA). After intramuscular vaccinations, these capsules function as an immunoticket to cultivate peripheral dendritic cells (DCs) with gut-homing receptors (CCR9)...
June 12, 2018: Advanced Materials
W Reid Bolus, Alyssa H Hasty
A critical contributor to health consequences of the obesity epidemic is dysregulated adipose tissue (AT) homeostasis. While white, brown, and beige AT function are all altered in obesity-related disease, white AT is marked by progressive inflammation & adipocyte dysfunction and has been the focus of extensive immunometabolism research in the past decade. The exact triggering events initiating and sustaining AT inflammation are still under study, but it has been shown that reducing inflammation improves insulin action in AT...
June 11, 2018: Journal of Lipid Research
Elia D Tait Wojno, Celine A Beamer
Innate lymphoid cells (ILCs) comprise a family of innate immune cells that orchestrate mucosal immune responses: initiating, sustaining, and even curbing immune responses. ILCs are relatively rare (≤1% of lymphocytes in mucosal tissues), lack classical cell-surface markers, and can be divided into three subsets (type 1-3 ILCs) based on differences in cytokine production, phenotype, and developmental pathway. Because ILCs can only be identified by combinations of cell-surface markers and cytokine production, multicolor flow cytometry is the most reliable method to purify, characterize, and assess the functionality of ILCs...
2018: Methods in Molecular Biology
Lunhua Liu, Karen Etsuko Inouye, Windy Rose Allman, Adam Steven Coleman, Shafiuddin Siddiqui, Gökhan Siddik Hotamisligil, Mustafa Akkoyunlu
Transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) is a receptor for the TNF superfamily cytokines, B cell activating factor (BAFF) and A Proliferation Inducing Ligand (APRIL). Here, we demonstrate that TACI-deficient mice subjected to high fat diet (HFD) are protected from weight gain and dysregulated glucose homeostasis. Resistance to HFD-induced metabolic changes in TACI-deficient mice does not involve TACI mediated adipogenesis. Instead, accumulation of M2 macrophages (Mϕs), eosinophils and type 2 innate lymphoid cells in visceral adipose tissue (VAT) is implicated in the protection from obesity induced assaults...
June 5, 2018: Diabetes
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