Innate lymphoid cells part II Flashcards
What group of ILCs are implicated in atopic dermatitis?
ILC2s.
What functions of ILC2s may contribute to Atopic dermatitis?
ILC2s activated by alarmins from the epithelium (IL-33, IL-25 and TSLP). They produce cytokines: IL-4, Il-5, Il-13.
Il-4 can recruit basophils and cause mast cell degranulation.
These cyotkines can potentially interact with epithelial cells, mast cells and basophils.
What group of ILCs are implicated with psoriasis?
ILC3s (IL-22 and IL17a) you see thickening of interfollicular epidermis and scaly plaques.
How might ILC cytokines promote psoriasis?
Il-22 (and to alesser extent IL-17) involved in epithelial proliferation,to drive thickening.
IL-17 can also drive neutrophil recruitment and inflammation.
Experimental indications IL-17 from ILCs is important in psoriasis?
NCR+ population of ILCs correlates with severity of the disease.
ILC3s and yD T cells rather than Th17 are the primary sources of Il-17 in mouse model of psoriasis with imiquimod.
What is imiquimod?
It is a TLR7 agonist applied to the skin of mice that induces symptoms of psoriasis.
What group of ILC2s important in asthma?
ILC2.
How might ILC2s contribute to asthma and airway inflammation?
Alarmins IL-33 and IL-25 that activate ILC2s are important in asthma. IL-13 goblet cell mucus production. Il-4 activation of basophils and mast cells. IL-5 expansion and recruitment of eosinophils. May drive Th2 responses and drive IgE class switch.
Although ICL2s may improve tissue repair post influenza infection by producing amphiregulin, how can they contribute to lung fibrosis>
Il-13 induces an M2 macrophage response and fibroblast activation. If exacerbated can inhibit wound healing and promote scarring.
What might happen to the ILC2 groups in COPD?
ILC2s may adopt an ILC1 phenotype that is damaging in patients.
Two diseases that make up IBD?
ulcerative colitis and crohns disease.
differences between UC and crohns?
UC involves only the colon. Crohns involves patches of the GI tract.
UC has mucosal inflammation, crohns inflammation is deeper.
Risk of colorectal cancer in UC (greater proliferation risk) not at risk of cancer in crohns.
What similarities between IL-23 and IL12?
cytokines share a common p40 subunit that binds to ac ommon chain of their receptor heterdimers.
In mouse model of colitis, Rag defient mice developed colitis. What does this mean?
Colitis can arise independently of T cells.
What happened in mouse model of colitis with Rag - mice, when anti-IL-23 ab added?
Colitis improved, suggesting that IL-23 responsive T cells (ILC3s) were promoting disease in T cell-deficient mice.
Whats a marker of lymphoid origin?
CD45.
What wer Sca1+ and Thy1 cells used to mark?
IL-23-responsive ILCs. Although Sca1+ now not specific for ILC3s Thy1+ also expressed by stromal cells?
What marker used for depletion of ILC3s in colitis?
Thy1+
what cytokines from ILC3s were driving colitis?
IL-17 and IFN-y and IL-22 implicated.
Il-17 levels were higher (2-3 fold) in colitis patients. What about IL-17 expression from ILCs?
Was increased 14 fold in this population.
What blocking anti-cytokine ab were most effective at reducing tumour formation in tumour RaG deficient mouse models? IFn-y, IL-17 or IL-22?
IL-22 blockade was as effective at blocking ILCs completely with Thy1 (CD90).
IL-17 and IFn-y blockade did reduce tumour incidence, but not as effectively.
In PSC liver disease, these patients also present with subclinical non-inflammatory IBD. Furthermore, PSC patients have an increased risk of colorectal cancer vs UC patients.
What frequencies of ILCs did they show?
Showed a higher accumulation of ILCs vs UC and controls. Whether IL-22 production of ILCs is responsible (non-inflammatory) might be interesting.
How might ILC3s have tolerogenic effects?
IL-1B from macrophages may stimulate ILC3s to produce GM-CSF which induces RA production in macrophages/DCs, promotes Tregs.
How might ILC3s control commensals?
DCs that sample lumen and produce IL-23 stimulates IL-22 production in ILC3s.This acts of panneth cells for AMP production and stimulates further IL-23 DC production.
Why is relevance of ILCs questionable?
Because data is correlative, and done in mice where T and B cells deficient -not physiological.
What innate features of ILCs might prove their relevance along with T cell responses?
At tissue sites and can produce rapid responses so early effectors.
What does lymphotoxin and GM-CSF production of ILCs do (T cells don’t produce these).
GC-MSF may be tolerogenic.
lymphotoxin (LN organogenesis) may enhance IgA protective responses in the gut.
Patients with SCID often only have cells of innate immune system. Often also lack NK cells. What cells were these patients also deficient in post transplant?
Still deficient in NK and ILCs.
Although patients with SCID treated with HSCT were not clinically immunodeficient, they still lack ILCs and NK cells. why might ILCs still be relevant?
Small cohort, may not be exposed to infections e.g. parasitic infections where ILCs important.
On antibiotics whilst T and B cells were reconstitutied. This may be window where ILCs important.
Unknown long term is more susceptible to cancers? (NK cells play important role, do ILCs?)
