scholarly journals Subset- and tissue-defined STAT5 thresholds control homeostasis and function of innate lymphoid cells

2017 ◽  
Vol 214 (10) ◽  
pp. 2999-3014 ◽  
Author(s):  
Alejandro V. Villarino ◽  
Giuseppe Sciumè ◽  
Fred P. Davis ◽  
Shigeru Iwata ◽  
Beatrice Zitti ◽  
...  
Keyword(s):  
Nk Cells ◽  
Gene Signature ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Barrier Integrity ◽  
Central Node ◽  
Genome Wide ◽  
Genetic Tuning ◽  
And Function ◽  
Environmental Interfaces

Innate lymphoid cells (ILCs) patrol environmental interfaces to defend against infection and protect barrier integrity. Using a genetic tuning model, we demonstrate that the signal-dependent transcription factor (TF) STAT5 is critical for accumulation of all known ILC subsets in mice and reveal a hierarchy of STAT5 dependency for populating lymphoid and nonlymphoid tissues. We apply transcriptome and genomic distribution analyses to define a STAT5 gene signature in natural killer (NK) cells, the prototypical ILC subset, and provide a systems-based molecular rationale for its key functions downstream of IL-15. We also uncover surprising features of STAT5 behavior, most notably the wholesale redistribution that occurs when NK cells shift from tonic signaling to acute cytokine-driven signaling, and genome-wide coordination with T-bet, another key TF in ILC biology. Collectively, our data position STAT5 as a central node in the TF network that instructs ILC development, homeostasis, and function and provide mechanistic insights on how it works at cellular and molecular levels.

scholarly journals Transcription Factors in the Development and Function of Group 2 Innate Lymphoid Cells

2019 ◽  
Vol 20 (6) ◽  
pp. 1377 ◽  
Author(s):  
Takashi Ebihara ◽  
Ichiro Taniuchi
Keyword(s):  
Transcription Factors ◽  
Physiological State ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Th2 Cytokine ◽  
Parasitic Worm ◽  
Group 2 ◽  
And Function

Group 2 innate lymphoid cells (ILC2s) are tissue-resident cells and are a major source of innate TH2 cytokine secretion upon allergen exposure or parasitic-worm infection. Accumulating studies have revealed that transcription factors, including GATA-3, Bcl11b, Gfi1, RORα, and Ets-1, play a role in ILC2 differentiation. Recent reports have further revealed that the characteristics and functions of ILC2 are influenced by the physiological state of the tissues. Specifically, the type of inflammation strongly affects the ILC2 phenotype in tissues. Inhibitory ILC2s, memory-like ILC2s, and ex-ILC2s with ILC1 features acquire their characteristic properties following exposure to their specific inflammatory environment. We have recently reported a new ILC2 population, designated as exhausted-like ILC2s, which emerges after a severe allergic inflammation. Exhausted-like ILC2s are featured with low reactivity and high expression of inhibitory receptors. Therefore, for a more comprehensive understanding of ILC2 function and differentiation, we review the recent knowledge of transcriptional regulation of ILC2 differentiation and discuss the roles of the Runx transcription factor in controlling the emergence of exhausted-like ILC2s. The concept of exhausted-like ILC2s sheds a light on a new aspect of ILC2 biology in allergic diseases.

scholarly journals The role of donor‐unrestricted T‐cells, innate lymphoid cells, and NK cells in anti‐mycobacterial immunity

2021 ◽  
Author(s):  
Paula Ruibal ◽  
Linda Voogd ◽  
Simone A. Joosten ◽  
Tom H. M. Ottenhoff
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells

NKR-P1B Receptor Expression and Function in the Different Innate Lymphoid Cells of the Lung

2021 ◽  
Author(s):  
Lucas Vajko
Keyword(s):  
Nk Cell ◽  
Γδ T Cells ◽  
Bronchial Epithelium ◽  
Lung Parenchyma ◽  
Recognition System ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Receptor Expression ◽  
And Function ◽  
Deficient Mice

Group 2 innate lymphoid cells (ILC2) are the majority of ILCs in murine lungs at steady state. ILC2s are the main producer of type-2-cytokines, IL-4, IL-5, IL-9, IL-13, and amphiregulin, playing key roles in lung tissue homeostasis, airway responses to pathogens and allergens, and in cancer-related defenses. ILC functions are regulated by cell surface receptors. NKR-P1B is an inhibitory receptor, which recognizes C-type lectin-related protein (Clr-b) as its ligand. NKR-P1B is expressed on subsets of natural killer cells, ILC2, ILC3, γδ T cells, macrophages and dendritic cells in a tissue-specific manner and regulates NK cell and ILC3 functions in the gut. Expression and function of NKR-P1B in the lung ILC populations is unexplored. Moreover, Clr-b, the ligand for NKR-P1B, is expressed in the bronchial epithelium, endothelial cells and in lung parenchyma, but its role in immune regulation in the lung is unknown. We hypothesize that ILC2s in the lung express NKR-P1B, and their function is regulated by the NKR-P1B:Clr-b recognition system. Using wild-type (WT) and NKR-P1B-deficient mice, we study the expression of NKR-P1B on lung ILC2, and the function of NKR-P1B:Clr-b recognition system in ILC2 development and function. We compare the phenotype, frequency, numbers and cytokine production by ILC2s upon stimulation between WT and NKR-P1B-deficient mice using antibody staining and flow cytometry analysis. This study will reveal the role of NKR-P1B as a model system for its human homolog, NKR-P1A, in the regulation of ILC development and function, advancing our understanding of how immune responses in the lung are regulated.

scholarly journals Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline

2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Ivan Ting Hin Fung ◽  
Poornima Sankar ◽  
Yuanyue Zhang ◽  
Lisa S. Robison ◽  
Xiuli Zhao ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Brain Physiology ◽  
Aged Brain ◽  
Group 2 ◽  
Resident Group ◽  
And Function

Increasing evidence has challenged the traditional view about the immune privilege of the brain, but the precise roles of immune cells in regulating brain physiology and function remain poorly understood. Here, we report that tissue-resident group 2 innate lymphoid cells (ILC2) accumulate in the choroid plexus of aged brains. ILC2 in the aged brain are long-lived, are relatively resistant to cellular senescence and exhaustion, and are capable of switching between cell cycle dormancy and proliferation. They are functionally quiescent at homeostasis but can be activated by IL-33 to produce large amounts of type 2 cytokines and other effector molecules in vitro and in vivo. Intracerebroventricular transfer of activated ILC2 revitalized the aged brain and enhanced the cognitive function of aged mice. Administration of IL-5, a major ILC2 product, was sufficient to repress aging-associated neuroinflammation and alleviate aging-associated cognitive decline. Targeting ILC2 in the aged brain may provide new avenues to combat aging-associated neurodegenerative disorders.

scholarly journals G9a regulates group 2 innate lymphoid cell development by repressing the group 3 innate lymphoid cell program

2016 ◽  
Vol 213 (7) ◽  
pp. 1153-1162 ◽  
Author(s):  
Frann Antignano ◽  
Mitchell Braam ◽  
Michael R. Hughes ◽  
Alistair L. Chenery ◽  
Kyle Burrows ◽  
...  
Keyword(s):  
Lymphoid Cell ◽  
Lymphoid Cells ◽  
Innate Lymphoid Cell ◽  
Genome Wide ◽  
Allergic Lung Inflammation ◽  
Severe Reduction ◽  
Repressive Histone Mark ◽  
Lysine Methyltransferase ◽  
Group 2 ◽  
And Function

Innate lymphoid cells (ILCs) are emerging as important regulators of homeostatic and disease-associated immune processes. Despite recent advances in defining the molecular pathways that control development and function of ILCs, the epigenetic mechanisms that regulate ILC biology are unknown. Here, we identify a role for the lysine methyltransferase G9a in regulating ILC2 development and function. Mice with a hematopoietic cell–specific deletion of G9a (Vav.G9a−/− mice) have a severe reduction in ILC2s in peripheral sites, associated with impaired development of immature ILC2s in the bone marrow. Accordingly, Vav.G9a−/− mice are resistant to the development of allergic lung inflammation. G9a-dependent dimethylation of histone 3 lysine 9 (H3K9me2) is a repressive histone mark that is associated with gene silencing. Genome-wide expression analysis demonstrated that the absence of G9a led to increased expression of ILC3-associated genes in developing ILC2 populations. Further, we found high levels of G9a-dependent H3K9me2 at ILC3-specific genetic loci, demonstrating that G9a-mediated repression of ILC3-associated genes is critical for the optimal development of ILC2s. Together, these results provide the first identification of an epigenetic regulatory mechanism in ILC development and function.

scholarly journals NK Cells Alleviate Lung Inflammation by Negatively Regulating Group 2 Innate Lymphoid Cells

2017 ◽  
Vol 198 (8) ◽  
pp. 3336-3344 ◽  
Author(s):  
Jiacheng Bi ◽  
Lulu Cui ◽  
Guang Yu ◽  
Xiaolu Yang ◽  
Youhai Chen ◽  
...  
Keyword(s):  
Nk Cells ◽  
Lung Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells

2017 ◽  
Vol 18 (9) ◽  
pp. 1004-1015 ◽  
Author(s):  
Yulong Gao ◽  
Fernando Souza-Fonseca-Guimaraes ◽  
Tobias Bald ◽  
Susanna S Ng ◽  
Arabella Young ◽  
...  
Keyword(s):  
Nk Cells ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells
Sign in / Sign up

Export Citation Format

Share Document