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.

Regulating the development of pulmonary Group 2 innate lymphoid cells

2019 ◽  
Vol 400 (11) ◽  
pp. 1497-1507 ◽  
Author(s):  
Sofia Helfrich ◽  
Claudia U. Duerr
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Morphological Changes ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
The Family ◽  
Intrinsic Regulation ◽  
Group 2 ◽  
And Function

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.

scholarly journals Localization and site-specific cell–cell interactions of group 2 innate lymphoid cells

2021 ◽  
Author(s):  
Kiniwa Tsuyoshi ◽  
Kazuyo Moro
Keyword(s):  
Lipid Production ◽  
Allergic Diseases ◽  
Innate Lymphoid Cells ◽  
The Body ◽  
Cell Interactions ◽  
Lymphoid Cells ◽  
Specific Cell ◽  
Inflammatory Conditions ◽  
Group 2 ◽  
Cell Cell

Abstract Group 2 innate lymphoid cells (ILC2s) are novel lymphocytes discovered in 2010. Unlike T or B cells, ILC2s are activated nonspecifically by environmental factors and produce various cytokines, thus playing a role in tissue homeostasis, diseases including allergic diseases, and parasite elimination. ILC2s were first reported as cells abundantly present in fat-associated lymphoid clusters in adipose tissue. However, subsequent studies revealed their presence in various tissues throughout the body, acting as key players in tissue-specific diseases. Recent histologic analyses revealed that ILC2s are concentrated in specific regions in tissues, such as the lamina propria and perivascular regions, with their function being controlled by the surrounding cells, such as epithelial cells and other immune cells, via cytokine and lipid production or by cell–cell interactions through surface molecules. Especially, some stromal cells are identified as the niche cells for ILC2s, both in the steady state and under inflammatory conditions, through the production of IL-33 or extracellular-matrix factors. Additionally, peripheral neurons reportedly co-localize with ILC2s and alter their function directly through neurotransmitters. These findings suggest that the different localizations or different cell–cell interactions might affect the function of ILC2s. Furthermore, generally, ILC2s are thought to be tissue-resident cells; however, they occasionally migrate to other tissues and perform a new role; this supports the importance of the microenvironment for their function. We summarize here the current understanding of how the microenvironment controls ILC2 localization and function with the aim of promoting the development of novel diagnostic and therapeutic methods.

scholarly journals Effects of BMP7 produced by group 2 innate lymphoid cells on adipogenesis

2020 ◽  
Vol 32 (6) ◽  
pp. 407-419 ◽  
Author(s):  
Yurina Miyajima ◽  
Kafi N Ealey ◽  
Yasutaka Motomura ◽  
Miho Mochizuki ◽  
Natsuki Takeno ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Adipocyte Differentiation ◽  
Allergic Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Brown Adipocytes ◽  
Morphogenetic Protein ◽  
Group 2

Abstract Group 2 innate lymphoid cells (ILC2s) are type 2 cytokine-producing cells that have important roles in helminth infection and allergic inflammation. ILC2s are tissue-resident cells, and their phenotypes and roles are regulated by tissue-specific environmental factors. While the role of ILC2s in the lung, intestine and bone marrow has been elucidated in many studies, their role in adipose tissues is still unclear. Here, we report on the role of ILC2-derived bone morphogenetic protein 7 (BMP7) in adipocyte differentiation and lipid accumulation. Co-culture of fat-derived ILC2s with pluripotent mesenchymal C3H10T1/2 cells and committed white preadipocyte 3T3-L1 cells resulted in their differentiation to adipocytes and induced lipid accumulation. Co-culture experiments using BMP7-deficient ILC2s revealed that BMP7, produced by ILC2s, induces differentiation into brown adipocytes. Our results demonstrate that BMP7, produced by ILC2s, affects adipocyte differentiation, particularly in brown adipocytes.

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.

Human innate lymphoid cells

Blood ◽  
2014 ◽  
Vol 124 (5) ◽  
pp. 700-709 ◽  
Author(s):  
Mette D. Hazenberg ◽  
Hergen Spits
Keyword(s):  
Interferon Γ ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Interleukin 5 ◽  
Type 2 Cytokines ◽  
Lymphoid Tissue Inducer Cells ◽  
Health And Disease ◽  
Group 2 ◽  
And Function ◽  
Regulatory Functions

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.

scholarly journals T-bet fate mapping identifies a novel ILC1-ILC2 subset in vivo

2020 ◽  
Author(s):  
J-H Schroeder ◽  
N Garrido-Mesa ◽  
T Zabinski ◽  
AL Gallagher ◽  
L Campbell ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Immune Responses ◽  
Critical Role ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Fate Mapping ◽  
Functional Roles ◽  
Mucosal Surfaces ◽  
Group 2

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.

More blurred lines with innate lymphoid cells

2019 ◽  
Vol 11 (502) ◽  
pp. eaay3577
Author(s):  
Patrick M. Brunner
Keyword(s):  
Allergic Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Group 2

Group 2 innate lymphoid cells might form a pool of innate cells with capabilities beyond fighting parasites and mediating allergic diseases.

scholarly journals IL-25 simultaneously elicits distinct populations of innate lymphoid cells and multipotent progenitor type 2 (MPPtype2) cells

2013 ◽  
Vol 210 (9) ◽  
pp. 1823-1837 ◽  
Author(s):  
Steven A. Saenz ◽  
Mark C. Siracusa ◽  
Laurel A. Monticelli ◽  
Carly G.K. Ziegler ◽  
Brian S. Kim ◽  
...  
Keyword(s):  
Immune Cell ◽  
Extramedullary Hematopoiesis ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Cell Populations ◽  
Helper Cells ◽  
Th2 Cytokine ◽  
Natural Helper ◽  
Group 2

The predominantly epithelial cell–derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) can promote CD4+ Th2 cell–dependent immunity, inflammation, and tissue repair at barrier surfaces through the induction of multiple innate immune cell populations. IL-25 and IL-33 were previously shown to elicit four innate cell populations, named natural helper cells, nuocytes, innate type 2 helper cells, and multipotent progenitor type 2 (MPPtype2) cells, now collectively termed group 2 innate lymphoid cells (ILC2). In contrast to other types of ILC2, MPPtype2 cells exhibit multipotent potential and do not express T1/ST2 or IL-7Rα, suggesting that MPPtype2 cells may be a distinct population. Here, we show that IL-33 elicits robust ILC2 responses, whereas IL-25 predominantly promotes MPPtype2 cell responses at multiple tissue sites with limited effects on ILC2 responses. MPPtype2 cells were distinguished from ILC2 by their differential developmental requirements for specific transcription factors, distinct genome-wide transcriptional profile, and functional potential. Furthermore, IL-25–induced MPPtype2 cells promoted Th2 cytokine–associated inflammation after depletion of ILC2. These findings indicate that IL-25 simultaneously elicits phenotypically and functionally distinct innate lymphoid– and nonlymphoid-associated cell populations and implicate IL-25–elicited MPPtype2 cells and extramedullary hematopoiesis in the promotion of Th2 cytokine responses at mucosal surfaces.

Sign in / Sign up

Export Citation Format

Share Document