NK and ILCs Flashcards
What TF regulates the activity of NK cells?
Eomes
describe the main features of ILC1
T-bet dependent
present before birth
secrete IFNy/TNF
describe the main features of ILC2
GATA3-dependent
secrete Th2 cytokines (IL4,5,9,13)
describe the main features of ILC3
RORyT-dependent
secrete IL-17 and 22 (Type 17 cytokines)
describe the role of LTis
Interact with stromal cells to promote SLO organogenesis and recruitment of immune cells.
Secrete IL-17 in the developing foetus
Secrete IL-22 in the adult
describe the main features of ILCregs
Poorly studied
No FoxP3 expression
secrete TGF-B and IL-10
How does the plasticity of ILCs compare to the one of CD4+ T cells?
ILCs displaying intermediate phenotypes have been described, similarly to CD4+ T cells.
Under extensive selective pressure in vitro (cytokines) plasticity is observed and transitions from one phenotype to another are observedb
Where do ILCs accumulate? How is this relevant to their function?
They accumulate lymphoid clusters (Crypto, Peyer’s caecal).
They are a relatively small population of cells, but by clustering they are able to influence surrounding DCs to prime a potent immune response.
How do you identify ILCs by FC?
IL-7R+
CD19/CD21- (B cell markers)
CD3- (T cell marker)
CD94(KIR)- (NK marker)
What progenitor do ILC 1,2 and 3 originate from?
Common helper ILC progenitor
What progenitor do NK, LTi and ILCreg originate from
Common ILC progenitor
Similarities and differences between Th1 and ILC1
ILC1 are involved in the early phase response against intracellular pathogens
Th1 cells provide a specific adaptive response and retain the potential to develop into memory T cells.
Both cells produce cytokines that are able to activate other immune cells
Describe the cross-talk between ILC2 and Th2
Both are involved in the clearance of extracellular parasites. They interact though the TCR/MHC axis=> Th2s make IL-2 which stimulates ILC2s to enhance IL-13 production (increased mucus secretion by goblet cells)
What subset of ILCs is involved in atopic dermatitis?
ILC2 frequency is higher in the skin lesions of patients with atopic dermatitis. Upregulation of IL-35 and IL-23 is found in these patients.
What subset of ILCs is involved is psiorasis?
ILC3.
What subsets of ILC2 is involved in airway inflammatory disorders?
ILC2.
Describe the ILC response in colitis and what major cytokine is involved in the process
ILCs resembling LTis but expressing RORyT that are responsive to IL-23 in the gut drive colitis; they increase the expression of IL-17 and IFN-y=> they drive the colitis
Describe the role of the Th17 response in IBD
Th17 genes are overexpressed.
IL-17 production is upregulated in ILCs
Describe the role of the ILC3 response in Crohn’s
Increased frequency of Il-23 responsive, IL-17 producing ILCs
Describe the role of ILCs in cancer
TheY support bacterial-induced colon cancer.
Apart from defense against pathogens and involvement in immunopathology, and SLO organogenesis, list other roles of ILCs
Regulation of adiposity and wound healing.