New type of immune cell discovered in the brain, links with gut

[natasa778]

http://neurosciencenews.com/immune-cell-gut-brain-5770/

The cells, known as “type 2 innate lymphocytes,” previously have been found in the gut, lung and skin – the body’s barriers to disease. Their discovery in the meninges, the membranes surrounding the brain, comes as a surprise. They were found as UVA researcher Jonathan Kipnis, PhD, explored the implications of his lab’s game-changing discovery last year that the brain and the immune system are directly connected via vessels long thought not to exist.

“This all comes down to immune system and brain interaction,” said Kipnis, chairman of UVA’s Department of Neuroscience. “The two were believed to be completely not communicating, but now we’re slowly, slowly filling in this puzzle. Not only are these [immune] cells present in the areas near the brain, they are integral to its function. When the brain is injured, when the spinal cord is injured, without them, the recovery is much, much worse.”

Curiously, the immune cells were found along the vessels discovered by Kipnis’ team. “They’re right on the lymphatics, which is really weird,” noted researcher Sachin Gadani. “You have the lymphatics and they’re stacked right on top. They’re not inside of them – they’re around them.”

 

[lansbergen]

http://jem.rupress.org/content/early/2016/12/16/jem.20161982

Brief Definitive Report
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury
Sachin P. Gadani, View ORCID ProfileIgor Smirnov, View ORCID ProfileAshtyn T. Smith, Christopher C. Overall, Jonathan Kipnis
DOI: 10.1084/jem.20161982 | Published December 19, 2016

Abstract
The meningeal space is occupied by a diverse repertoire of immune cells. Central nervous system (CNS) injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation remains poorly understood. Here, we describe type 2 innate lymphocytes (ILC2s) as a novel cell type resident in the healthy meninges that are activated after CNS injury. ILC2s are present throughout the naive mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile. After spinal cord injury (SCI), meningeal ILC2s are activated in an IL-33–dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild-type lung-derived ILC2s into the meningeal space of IL-33R−/− animals partially improves recovery after SCI. These data characterize ILC2s as a novel meningeal cell type that responds to SCI and could lead to new therapeutic insights for neuroinflammatory conditions.

 

[lansbergen]

https://en.wikipedia.org/wiki/Innate_lymphoid_cell

Group 2 ILCs
Group 2 ILCs can produce type 2 cytokines (e.g. IL-4, IL-5, IL-9, IL-13).

ILC2s (also termed natural helper cells, nuocytes, or innate helper 2 cells[6] ) play the crucial role of secreting type 2 cytokines in response to helminth infection. They have also been implicated in the development of allergic lung inflammation. They express characteristic surface markers and receptors for chemokines, which are involved in distribution of lymphoid cells to specific organ sites. They require IL-7 for their development, which activates two transcription factors (both required by these cells)—RORα and GATA3. ILC2s are critical for primary responses to local Th2 antigens in the lung but are dispensable for responses to systemically delivered Th2 antigens.[7]

 

[roller]

ILCs are a multifunctional group of cells. Their ability to rapidly secrete immunoregulatory cytokines allows them to contribute early on in immune responses to infection. They often reside at mucosal surfaces, where they are exposed to infectious agents in the environment.

Helminth infection[edit]
ILC2 cells play a crucial role in the protection against helminthic infection. They are a major early source of IL-13, which can activate T cells and induce physiological responses that will help expel a parasite. These physiological responses include stimulating goblet cell mucus secretion and contraction of smooth muscle. In addition, they secrete signals that recruit and activate mast cells and eosinophils, and which stimulate B cell proliferation. They also secrete Amphiregulin, a member of the epidermal growth factor family, that stimulates tissue repair. This can function to enhance the barrier function of the epithelium and slow pathogen entry.[12]

https://en.wikipedia.org/wiki/Innate_lymphoid_cell

 

[trishrhymes]

I see this research was done on mice. It will be interesting to see whether it's possible to find the same in humans.

 

[lansbergen]

I see this research was done on mice. It will be interesting to see whether it's possible to find the same in humans.

Postmortum or when meninges are taken for other purposes.

 

[thegodofpleasure]

University of Virginia Health System Press statement (19/12/2016)

Unknown soldiers: UVA discovers powerful defenders of the brain
http://newsroom.uvahealth.com/about...uva-discovers-powerful-defenders-of-the-brain

 

[TiredSam]

University of Virginia Health System Press statement (19/12/2016)

Unknown soldiers: UVA discovers powerful defenders of the brain
http://newsroom.uvahealth.com/about...uva-discovers-powerful-defenders-of-the-brain

Excellent article - attention-grabbing headline and clear enough for dummies to understand .

 

[jepps]

University of Virginia Health System Press statement (19/12/2016)

Unknown soldiers: UVA discovers powerful defenders of the brain
http://newsroom.uvahealth.com/about...uva-discovers-powerful-defenders-of-the-brain

The microbes regulate the innate lymphoid cells:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3495160/

Commensal bacteria indirectly regulate ILCs through myeloid cells and epithelial cells
In addition to direct regulation, commensal bacteria can indirectly regulate ILCs through modulation of myeloid cell or epithelial cell responses. Recent evidence has demonstrated that commensal bacteria are essential for optimal antiviral immunity, in part through promoting optimal pro-inflammatory cytokine responses in mononuclear phagocytes (Abt et al., 2012; Ganal et al., 2012; Ichinohe et al., 2011).

In one report, commensal bacteria modulated mononuclear phagocytes through Myd88, Trif and epigenetic pathways to promote IL-6, IL-12, IL-15, TNFα and type 1 interferon production which was essential to promote optimal NK cell responses (Ganal et al., 2012). Additional reports have implicated that commensal bacteria within the Lactobacillus genus can induce IFNγ and cytolytic responses in intestinal NK cells through engagement of TLR2 and TLR4 on dendritic cells (DCs) and subsequent induction of IL-12 (Fink et al., 2007; Koizumi et al., 2008) (Figure 2B, right).