Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE

Hatfield, Julianne K.; Brown, Melissa A.

doi:10.1016/j.cellimm.2015.06.006

Cited by 58 publications

(68 citation statements)

References 77 publications

(135 reference statements)

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“… 40 Notably, recent evidence also argues that γδT cells are a normal component of the meninges in C57bl/6 mice. 41 Furthermore, the rapid increases in γδT-cell mRNA levels and γδT-cell–positive IHC stains in the mouse brain at 6 hours after HI suggest that γδT cells in the neonatal mouse brain are innate subsets and perhaps some of the γδT cells are already resident in the brain or near the brain. However, the possibility of trafficking of peripheral γδT cells into the brain in response to injury cannot be completely ruled out.…”

Section: Discussionmentioning

confidence: 99%

γδ T Cells Contribute to Injury in the Developing Brain

Albertsson

Zhang

Vontell

et al. 2018

The American Journal of Pathology

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Brain injury in premature infants, especially periventricular leukomalacia, is an important cause of neurologic disabilities. Inflammation contributes to perinatal brain injury development, but the essential mediators that lead to early-life brain injury remain largely unknown. Neonates have reduced capacity for mounting conventional αβT-cell responses. However, γδT cells are already functionally competent during early development and are important in early-life immunity. We investigated the potential contribution of γδT cells to preterm brain injury using postmortem brains from human preterm infants with periventricular leukomalacia and two animal models of preterm brain injury—the hypoxic-ischemic mouse model and a fetal sheep asphyxia model. Large numbers of γδT cells were observed in the brains of mice, sheep, and postmortem preterm infants after injury, and depletion of γδT cells provided protection in the mouse model. The common γδT-cell–associated cytokines interferon-γ and IL-17A were not detectable in the brain. Although there were increased mRNA levels of Il17f and Il22 in the mouse brains after injury, neither IL-17F nor IL-22 cytokines contributed to preterm brain injury. These findings highlight unique features of injury in the developing brain, where, unlike injury in the mature brain, γδT cells function as initiators of injury independently of common γδT-cell–associated cytokines. This finding will help to identify therapeutic targets for preventing or treating preterm infants with brain injury.

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Section: Discussionmentioning

confidence: 99%

γδ T Cells Contribute to Injury in the Developing Brain

Albertsson

Zhang

Vontell

et al. 2018

The American Journal of Pathology

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“…Although ILCs are predominantly found at mucosal barriers, including the lung, gut, skin and uterus, they are also present in other tissues, such as adipose tissue, liver and meninges. The relative proportions of different ILC types are distinct in each tissue, likely reflecting the unique homeostatic requirements of the tissue.…”

Section: Discovery and Function Of Ilc Subsetsmentioning

confidence: 99%

Type 2 innate lymphoid cells in the induction and resolution of tissue inflammation

Wallrapp

Riesenfeld

Burkett

et al. 2018

Immunological Reviews

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Summary Type 2 immunity against pathogens is tightly regulated to ensure appropriate inflammatory responses that clear infection and prevent excessive tissue damage. Recent research has shown that type 2 innate lymphoid cells (ILC2s) contribute to steady‐state tissue integrity and exert tissue‐specific functions. However, upon exposure to inflammatory stimuli, they also initiate and amplify type 2 inflammation by inducing mucus production, eosinophilia, and Th2 differentiation. In this review, we discuss the regulation of ILC2 activation by transcription factors and metabolic pathways, as well as by extrinsic signals such as cytokines, lipid mediators, hormones, and neuropeptides. We also review recent discoveries about ILC2 plasticity and heterogeneity in different tissues, as revealed partly through single‐cell RNA sequencing of transcriptional responses to various stimuli. Understanding the tissue‐specific pathways that regulate ILC2 diversity and function is a critical step in the development of potential therapies for allergic diseases.

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“…In the context of lymphoneogenesis in the adult host, distinct cell types may substitute as TLT inducer and organizer cells. LTi equivalent cell types implicated in TLT formation include: innate lymphoid cells ( 21 – 23 ), T cells ( 24 – 27 ), NKT cells ( 28 ), as well a myeloid cells ( 28 , 29 ). Although the exact combination of molecular cues may differ, a unifying feature of TLT-inducing leukocytes is their production of cytokines, especially IL-17 [reviewed by Ref.…”

Section: Tertiary Lymphoid Tissuesmentioning

confidence: 99%

Meningeal Tertiary Lymphoid Tissues and Multiple Sclerosis: A Gathering Place for Diverse Types of Immune Cells during CNS Autoimmunity

et al. 2016

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Collections of leukocytes in the meningeal space have been documented in Multiple Sclerosis (MS). These meningeal aggregates, which in the context of other autoimmune diseases have often been termed tertiary lymphoid tissues (TLT), have been associated with sub-pial cortical damage and disease progression. However, the key molecular and cellular signals required for their formation and maintenance remain unclear. Herein, we review TLT structures in other disease states in order to provide a framework for understanding these structures in the MS meninges. We then assess the evidence that the meningeal compartment serves as an important nexus for immune cells as well as a location for drainage of antigen into cervical lymph nodes. Extrapolating what is known about the molecular and cellular cues that initiate the formation of leukocyte aggregates in non-lymphoid tissues, we speculate on what signals lead to the formation and maintenance of meningeal TLT structures. Referring to the animal model of MS [experimental autoimmune encephalomyelitis (EAE)], we also explore what is known about these structures in supporting B cell and T cell responses during neuroinflammation. Last, we examine the evidence that connects these structures to ongoing neuropathology. Collectively, our review points to the meningeal compartment as an important player in neuroinflammatory processes. Moreover, we hypothesize that in order to gain insights into pro- and anti-inflammatory properties of lymphocytes in MS, one must understand the cellular scaffolds that support lymphocyte retention within the meninges, thus highlighting the importance of non-immune cells (stromal cells) in the neuroinflammatory process.

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Group 3 innate lymphoid cells accumulate and exhibit disease-induced activation in the meninges in EAE

Cited by 58 publications

References 77 publications

γδ T Cells Contribute to Injury in the Developing Brain

γδ T Cells Contribute to Injury in the Developing Brain

Type 2 innate lymphoid cells in the induction and resolution of tissue inflammation

Meningeal Tertiary Lymphoid Tissues and Multiple Sclerosis: A Gathering Place for Diverse Types of Immune Cells during CNS Autoimmunity

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