Flashcards in ILCs in Inflammatory Disease Deck (35):
What are the major roles of ILCs?
Roles in inflammatory diseases and in maintenance of gut microbiota.
Describe the asthmatic airway.
Increased inflammation in the bronchial tubes.
Describe the asthmatic airway during an asthma attack.
Increased swelling, tightening of the muscles in the airway, excess mucus production.
Give the main features of asthma.
Goblet cell hyperplasia, increased mucus production, increased ASM contractability and collagen deposition.
Give the cytokines released by lung epithelial cells that act upon ILC2s.
IL-33, IL-25 and TSLP.
Give examples of allergens involved in asthma.
Pollen and HDM Der p1 Cys protease.
Give the cytokines produced by eosinophils and basophils.
Eosinophils - IL-4 and IL-5
Basophils - IL-4 (activates ILC2s)
What does the functionality of mast cells depend on?
Their level of activation.
What happens when mast cells are activated by IL-33?
Mast cells activate Tregs to produce IL-10, which suppresses ILC2 activity.
How are mast cells fully activated?
By IgE crosslinking to FcεRI and degranulation.
What happens when mast cells are fully activated?
Mast cells produce lipid mediators, e.g. prostaglandin-2 - which activate ILC2s.
Give evidence for the importance of ILC2s in asthma.
- Rag2 -/- IL-2Ry -/- mice have less airway inflammation in papain/IL-33 induced asthma, due to lack of ILC2s.
- Adoptive transfer of ILC2s into these mice increases inflammation.
- Increased ILC2s associated with severe asthma.
- Increased ILC2-derived cytokines in sputum correlates with poorer respiratory function.
- Experienced ILC2s respond more vigorously to secondary challenge.
- Polymorphisms in IL-13/IL-13R associated to paediatric asthma.
What is chronic rhinosinusitis?
Condition where the sinus in the nasal cavity is swollen.
What cells are expanded in chronic rhinosinusitis?
Eosinophils and ILC2s - drive the inflammation.
How do eosinophils and ILC2s cross activate each other?
IL-4 released by eosnophils reinforces ILC2 action, resulting in increased IL-5 production from ILC2s, which activates eosinophils.
Give evidence for the importance of ILC2s in allergic responses.
Peripheral blood ILC2 levels are higher in patients with allergic rhinitis (hayfever), sensitised to HDM or grass pollen.
How can ILC2 levels be decreased in allergic rhinitis patients?
Through injection of small amounts of allergens - giving some desensitisation effects.
What is COPD?
COPD = Chronic Obstructive Pulmonary Disease
- group of lung conditions, including emphysema and chronic bronchitis.
What is the main cause of COPD?
How do lung ILC2s respond to cigarette smoke challenge in mouse models?
Respond to IL-12 and IL-18, released by lung epithelial cells, by downregulating GATA3 and upregulating T-bet and IFNy -> switch from ILC2 to ILC1 phenotype.
What is plasticity in the ILC2 phenotype due to?
Action of IL-1b on ILC2s.
How does the ratio of ILCs relate to COPD disease severity?
Higher ratio of ILC1s than ILC2s in COPD patient blood and lungs correlates with disease severity.
What does the ILC2 phenotypic switch occur in response to during COPD?
How does IFNy production contribute to COPD?
Stimulates lung epithelial cells to produce more ILC2-activating cytokines.
Give the two major ILC1 populations in the human gut.
- NCR- ILC1s (no NKp44) in the lamina propria.
- NKp44+ ILC1s (intraepithelial ILCs)
What cell population is expanded in Crohn's disease?
ILC1s - higher numbers associated with increased disease severity.
Why are ILC3s also significantly reduced in IBD patients?
ILC3s differentiate to give ILC1s in response to IL-12, released by DCs.
Towards which subtype does ILC plasticity tend to be?
Describe the ILC plasticities seen in IBD patients.
ILC3s -> ILC1s
ILC2s -> ILC1s
Describe the role of ILCs in liver damage and hepatic fibrosis.
Liver damage leads to IL-33 release, which results in accumulation of ILC2s in the liver.
Give evidence for the role of ILC2s in hepatic fibrosis.
- chronic schistomiasis infection is used to induce liver damage in mice.
- when mice are given thy1.2 ab that depletes ILCs, there is decreased collagen deposition and therefore decreased liver damage.
- addition of ILC2s by adoptive transfer showed standard disease progression.
Give examples of when ILCs are involved in inflammation of the skin.
ILC2s - associated with eczema.
ILC3s - associated with psoriasis.
Describe the role of ILCs in skin repair.
- Epidermal Notch-1 signalling recruits ILC3s to damaged skin.
- TNF helps localise the ILC3s.
- IL-17F produced by ILC3s helps to recruit macrophages.
- IL-33 expression and the ILC2 response are increased after cutaneous wounding.
Give evidence for the role of ILC2s in wound repair.
Mice given injection of IL-33 have increased ILC2s at the wound site, which produce IL-13 and IL-5 to enhance wound closure and re-epithelisation.
Mice lacking ILCs have inefficient wound repair.