NK and ILCs

Question 1

What TF regulates the activity of NK cells?

Answer 1

Eomes

Question 2

describe the main features of ILC1

Answer 2

T-bet dependent
present before birth
secrete IFNy/TNF

Question 3

describe the main features of ILC2

Answer 3

GATA3-dependent

secrete Th2 cytokines (IL4,5,9,13)

Question 4

describe the main features of ILC3

Answer 4

RORyT-dependent

secrete IL-17 and 22 (Type 17 cytokines)

Question 5

describe the role of LTis

Answer 5

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

Question 6

describe the main features of ILCregs

Answer 6

Poorly studied
No FoxP3 expression
secrete TGF-B and IL-10

Question 7

How does the plasticity of ILCs compare to the one of CD4+ T cells?

Answer 7

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

Question 8

Where do ILCs accumulate? How is this relevant to their function?

Answer 8

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.

Question 9

How do you identify ILCs by FC?

Answer 9

IL-7R+
CD19/CD21- (B cell markers)
CD3- (T cell marker)
CD94(KIR)- (NK marker)

Question 10

What progenitor do ILC 1,2 and 3 originate from?

Answer 10

Common helper ILC progenitor

Question 11

What progenitor do NK, LTi and ILCreg originate from

Answer 11

Common ILC progenitor

Question 12

Similarities and differences between Th1 and ILC1

Answer 12

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

Question 13

Describe the cross-talk between ILC2 and Th2

Answer 13

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)

Question 14

What subset of ILCs is involved in atopic dermatitis?

Answer 14

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.

Question 15

What subset of ILCs is involved is psiorasis?

Answer 15

ILC3.

Question 16

What subsets of ILC2 is involved in airway inflammatory disorders?

Answer 16

ILC2.

Question 17

Describe the ILC response in colitis and what major cytokine is involved in the process

Answer 17

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

Question 18

Describe the role of the Th17 response in IBD

Answer 18

Th17 genes are overexpressed.

IL-17 production is upregulated in ILCs

Question 19

Describe the role of the ILC3 response in Crohn’s

Answer 19

Increased frequency of Il-23 responsive, IL-17 producing ILCs

Question 20

Describe the role of ILCs in cancer

Answer 20

TheY support bacterial-induced colon cancer.

Question 21

Apart from defense against pathogens and involvement in immunopathology, and SLO organogenesis, list other roles of ILCs

Answer 21

Regulation of adiposity and wound healing.