scholarly journals Transcription factors controlling development and function of innate lymphoid cells

2014 ◽  
Vol 26 (3) ◽  
pp. 119-128 ◽  
Author(s):  
Y. Tanriver ◽  
A. Diefenbach
2019 ◽  
Vol 20 (6) ◽  
pp. 1377 ◽  
Author(s):  
Takashi Ebihara ◽  
Ichiro Taniuchi

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.


2019 ◽  
Vol 400 (11) ◽  
pp. 1497-1507 ◽  
Author(s):  
Sofia Helfrich ◽  
Claudia U. Duerr

Abstract Group 2 innate lymphoid cells (ILC2s) are members of the family of innate lymphoid cells and are innately committed to type 2 immune responses. In the lungs, ILC2s are the predominant population of innate lymphoid cells (ILCs) and their development is orchestrated by several different transcription factors ensuring lineage commitment by intrinsic regulation. ILC2s are present in the lungs from the foetal period onwards and are thus exposed to extrinsic regulation due to the airways’ continuous morphological changes upon birth. In this review, we will briefly summarise the dependence of ILC2s on transcription factors and discuss recently described characteristics and function of early life ILC2s in the lungs.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Chao Zhong ◽  
Jinfang Zhu

Recent studies on innate lymphoid cells (ILCs) have expanded our knowledge about the innate arm of the immune system. Helper-like ILCs share both the “innate” feature of conventional natural killer (cNK) cells and the “helper” feature of CD4+T helper (Th) cells. With this combination, helper-like ILCs are capable of initiating early immune responses similar to cNK cells, but via secretion of a set of effector cytokines similar to those produced by Th cells. Although many studies have revealed the functional similarity between helper-like ILCs and Th cells, some aspects of ILCs including the development of this lineage remain elusive. It is intriguing that the majority of transcription factors involved in multiple stages of T cell development, differentiation, and function also play critical roles during ILC development. Regulators such as Id2, GATA-3, Nfil3, TOX, and TCF-1 are expressed and function at various stages of ILC development. In this review, we will summarize the expression and functions of these transcription factors shared by ILCs and Th cells. We will also propose a complex transcriptional regulatory network for the lineage commitment of ILCs.


Author(s):  
Lucas Vajko

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.


2020 ◽  
Vol 217 (4) ◽  
Author(s):  
Ivan Ting Hin Fung ◽  
Poornima Sankar ◽  
Yuanyue Zhang ◽  
Lisa S. Robison ◽  
Xiuli Zhao ◽  
...  

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.


Nature ◽  
2013 ◽  
Vol 494 (7436) ◽  
pp. 261-265 ◽  
Author(s):  
Christoph S. N. Klose ◽  
Elina A. Kiss ◽  
Vera Schwierzeck ◽  
Karolina Ebert ◽  
Thomas Hoyler ◽  
...  

Blood ◽  
2014 ◽  
Vol 124 (5) ◽  
pp. 700-709 ◽  
Author(s):  
Mette D. Hazenberg ◽  
Hergen Spits

Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of particular transcription factors for their development and function. Group 1 ILCs (ILC1s) produce interferon γ and depend on Tbet, group 2 ILCs (ILC2s) produce type 2 cytokines like interleukin-5 (IL-5) and IL-13 and require GATA3, and group 3 ILCs (ILC3s) include lymphoid tissue inducer cells, produce IL-17 and/or IL-22, and are dependent on RORγt. Whereas ILCs play essential roles in the innate immune system, uncontrolled activation and proliferation of ILCs can contribute to inflammatory autoimmune diseases. In this review, we provide an overview of the characteristics of ILCs in the context of health and disease. We will focus on human ILCs but refer to mouse studies if needed to clarify aspects of ILC biology.


2020 ◽  
Author(s):  
J-H Schroeder ◽  
N Garrido-Mesa ◽  
T Zabinski ◽  
AL Gallagher ◽  
L Campbell ◽  
...  

ABSTRACTInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Various subsets exist resembling T cell lineages defined by the expression of specific transcription factors. Thus, T-bet is expressed in ILC1 and Th1 cells. In order to further understand the functional roles of T-bet in ILC, we generated a fate-mapping mouse model that permanently marks cells and their progeny that are expressing, or have ever expressed T-bet. Here we have identified and characterised a novel ILC with characteristics of ILC1 and ILC2 that are “fate-mapped” for T-bet expression and arise early in neonatal life prior to establishment of a mature microbiome. These ILC1-ILC2 cells are critically dependent on T-bet and are able to express type 1 and type 2 cytokines at steady state, but not in the context of inflammation. These findings refine our understanding of ILC lineage regulation and stability and have important implications for the understanding of ILC biology at mucosal surfaces.SUMMARYInnate lymphoid cells (ILC) play a critical role in regulating immune responses at mucosal surfaces. Three distinct ILC groups have been described according to expression of subset defining transcription factors and other markers. In this study we characterize a novel ILC subset with characteristics of group 1 and group 2 ILC in vivo.


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