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EV ACVD Study > ICADA Cytokines, Chemokines > Flashcards

ICADA Cytokines, Chemokines Flashcards

1
Q

Which test modality allows sequencing of the full transcriptome at the single-cell level

A

Next-generation sequencing (NGS)

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2
Q

What is the effect of protease processing on IL-33

A

IL-33 is always expressed and active, but when processed by proteases, it can become a shorter “hyperactive” form –> enhances allergic inflammation

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3
Q

IL-33 expression levels in acute and chronic cAD

A

High in cAD dogs, not present in healthy dogs

Associated with pruritus, excoriations

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4
Q

Keratinocyte (innate) receptor for HDM-derived proteases

A

PAR-2

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5
Q

Keratinocyte (innate) receptor for Staphylococcus membrane proteins

A

TLR 1/2

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6
Q

Which cytokine made by keratinocytes was found to be upregulated in acute cAD flares from HDM or Staphylococcal infections in 1 study, but mRNA was downregulated in another

A

TSLP

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7
Q

Potent chemoattractant for Th2 cells

A

TARC/CCL17

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8
Q

Receptor for TARC

A

CCR4

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9
Q

Which cells express CCR4

A

Th2 cells (TARC ligand is a chemoattractant for Th2)

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10
Q

Which cytokine is associated with cAD severity

A

TARC

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11
Q

What cytokine should be considered a biomarker for cAD?

A

TARC

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12
Q

Which medications have shown a reduction in TARC

A

*Prednisolone
*Apoquel

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13
Q

How are CCR4 inhibitors (TARC receptor) for cAD therapy?

A

Moderate reduction in CADESI, but not statistically significant.

May be d/t different cAD endotypes

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14
Q

Ligands for CCR4

A

TARC, MDC

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15
Q

T or F: Macrophage-derived chemokine (MDC) can recruit Th2 to inflammatory loci in cAD skin

A

True

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16
Q

T or F: high MDC level was associated with higher pVAS and CADESI scores in cAD dogs

A

True

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17
Q

Which cells secrete IL-4

A

*Th2
*Mast cells
*Eosinophils
*Basophils

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18
Q

Major functions of IL-4 (2)

A

*Th2 leukocyte survival
*IgE class switching of B cells

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19
Q

Are IL-4 levels different in cAD vs healthy skin

A

Conflicting studies

BUT

*IL-4 is increased in acute phase of cAD, but maybe not chronic cAD
*IL-4 R is increased in cAD skin

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20
Q

Cells that produce IL-5

A

*Th2
*Mast cells

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21
Q

Function of IL-5

A

*Survival, activation, migration of eosinophils

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22
Q

Is IL-5 increased or decreased in cAD skin

A

Increased

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23
Q

Receptor for IL-13

A

IL-4RA

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24
Q

Functions of IL-13

A

*IgE production
*Th2 differentiation

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25
Q

Is IL-13 increased or decreased in cAD

A

Increased

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26
Q

Mutations in which gene was associated with increased cAD in miniature dachshunds

A

IL-4Ra (IL-13, IL-4 bind)

When receptor was defective, less allergic inflammation, less cAD!!

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27
Q

Cells that make IL-31

A

Th2, T cells

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28
Q

Do cAD dogs have higher IL-31RA X1 (binds IL-31) or IL-31RA X2 (can’t bind)

A

ILRA X2 isoform

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29
Q

Where can you find IL-31RA?

A

*Dorsal root ganglion
*Nerve fibers in cAD epidermis

*Also keratinocytes

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30
Q

How does IL-31 cause itch?

A

Direct action on sensory neurons

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31
Q

T or F: IL-31 does not affect the skin barrier

A

F: Cytopoint decrease TEWL!

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32
Q

Are IL-31 levels increased or decreased with cAD?

A

Increased

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33
Q

Is there a correlation of cytokine mRNA and protein expression between skin and blood

A

No

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34
Q

When does IL-31 expression peak after allergy flare

A

24-48 hr later

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35
Q

What percent of dogs have prevention of itch/skin lesions for >1 year when using Cytopoitn proactively

A

28%

36
Q

Does the anti-IL-31 vaccine work to reduce itching to HDM allergens

A

Yes.

37
Q

Which cells make IFNg?

A

*Th1
*Tc
*NK cells

38
Q

Functions of IFNg

A

*Inhibits Th2
*Promotes Th1
*Increased APC ability
*Inhibit viral replication

39
Q

Level of IFNg in chronic cAD dogs

A

CONFLICTING. INCREASED in some studies, unaffected in many studies, reduced in others

A Th1 cytokine BUT we think IFNg is increased in chronic lesions

40
Q

Name 3 IFNg INDUCING factors

A

*IL-12
*IL-15
*IL-18

41
Q

Which subunit of IL-12 is a more specific inducer of Th1 (IL-12p35 or IL-12p40)

A

IL-12p40

42
Q

What is unique about IL-18 in the ABSENCE of IL-12

A

Stimulates both Th1 and Th2 responses

43
Q

What are the 3 cell surface molecules that define a Treg

A

*CD4
*CD25
*Foxp3

44
Q

Are IL-10 and TGF-b increased or decreased in cAD?

A

Conflicting studies!

*Likely a functional insufficiency of Treg cells in cAD

45
Q

Is IL-10 and TGFb increased or decreased after 1 year of ASIT?

A

No change

46
Q

Does the amount of IL-10 and TGFb correlate with ASIT treatment success

A

No

So we don’t even KNOW if ASIT works via affecting Tregs anymore!

47
Q

Which Th type is a potent producer of local tissue inflammation via upregulation of proinflammatory and neutrophil-mobilizing cytokines

A

Th17

48
Q

Cytokines made by Th17 cells

A

*IL-6
*granulocyte-macrophage colony=stimulating factor (GM-CSF)
*TNF-a
*IL-1b
*CXCL1
*MCP1
*MCP3
*MIP-3a
*MMPs

49
Q

Which Th is involved in psoriasis

A

Th17

50
Q

Which cells are activated by GM-CSF

A

Langerhan cells

51
Q

Which cells are chemoattracted by S100A8 and IL-8

A

Neutrophils

52
Q

Impact of IL-17 on S100A8 and IL-8

A

Increase, more neutrophil chemotaxis

53
Q

Does IL-17 signaling increased Th1 or Th2 more

A

Increased Th2 from IL-17 signaling more

(but also increases IFNg, which is Th1)

54
Q

Is IL-17 increased or decreased in cAD skin

A

No change

55
Q

Which cytokine is an activator of keratinocyte proliferation

A

IL-22

56
Q

Which cytokine can increase epidermal host defense peptides and neutrophil chemoattractants

A

IL-22

57
Q

Name 5 host defense peptides

A

*B-defensin
*Cathelicidin
*S100A8
*S100A9
*S100A7

58
Q

Is IL-22 increased or decreased in cAD skin?

A

Conflicting studies in dogs

In human AD, it is increased significantly in chronic lesions, but also present in acute lesions

59
Q

Cells that make IL-7

A

*Stromal cells of bone marrow, thymus
*Keratinocytes

60
Q

Function of IL-7

A

*Development of memory Th cells (crucial for cAD and asthma)

61
Q

Levels of IL-7 in cAD skin

A

Possibly increased! (one study)

62
Q

Cells that make IL-34

A
  • Keratinocytes
  • Neurons in brain
63
Q

Function of IL-34

A

Development of myeloid cells (LC in skin, microglia in brain)

64
Q

Level of IL-34 in human AD skin; in dogs

A

Humans: Decreased

IL-34 inhibits propagation of inflammatory cascade

Dogs: Increased, but unchanged even with successful tx.
Likely IL-34 unimportant for cAD

65
Q

Cells that make IL-36

A

*Barrier sites: bronchial, intestinal, dermal epithelium

66
Q

Is IL-36 immediately active when expressed?

A

No, needs N-terminus cleaved

67
Q

Function of IL-36

A

*Host defense against Staphylococcus
*Amplifies inflammatory response in skin

68
Q

Level of IL-36 in cAD skin

A

INCREASED

To help fight off Staphylococcus

69
Q

Cells that produces macrophage migration inhibitor factor (MIF)

A

Immune and nonimmune cells

70
Q

Function of MIF (macrophage inhibition factor)

A

*T cell activation
*Recruits/activates macrophages at inflammatory loci –> delayed-type hypersensitivity

71
Q

Level of MIF in cAD serum

A

HIGHER

BUT no association with CADESI or pVAS

72
Q

Vasodilation and leukocyte-mediated inflammation mediated by neruopeptides is called ________

A

Neurogenic inflammation;

Potentiates chronic cAD

73
Q

Cells that produce nerve growth factor (NGF)

A

Keratinocytes

74
Q

Function of nerve growth factor

A

Promote growth of nerve endings in skin –> neuronal sensitization

75
Q

Level of NGF in cAD vs healthy skin

A

HIGH NGF in cAD skin

76
Q

Which neuropeptide is associated with induction of cAD flares

A

Nerve growth factor

NOT changed in non-lesional skin though!

77
Q

Does mAB against NGF decrease cAD flares or pruritus?

A

No

78
Q

Cells that produce substance P

A

*Free nerve endings in skin
*Keratinocytes
*inflammatory cells

79
Q

Function of substance P

A

*Mediator of pruritus
*Can induce cutaneous inflammation

80
Q

Level of substance P in cAD skin

A

Increased

But not changed in nonlesional skin; not increased in acute experimental flare model

81
Q

Which medication substance p blocker is effective for pruritus and skin lesions in cats

A

Ceremia (SP receptor antagonist; blocks neurokinin 1 receptor)

82
Q

Receptor for substance P

A

1) Neurokinin 1 R
*Cerenia = NK1R antagonist
2) Mrgpr

ONLY Mrgpr IS RESPONSIBLE FOR PRURITUS
So it is possible an Mrgpr blocker would work better than cerenia

83
Q

Which cell produces periostin

A

Fibroblasts
Epithelial cells
Endothelial cells

84
Q

Which type of protein is periostin

A

Extracellular matrix protein

85
Q

Function of periostin

A

*Differentiation and migration of fibroblasts
*Proliferation of keratinocytes

Wound healing, remodeling, repair

*NEW: activates itch sensory neurons!!

86
Q

When cAD skin is cultured with IL-13, what happens to periostin levels

A

Increased –> mnore itch!

Periostin may increased Th2 cytokines

87
Q

Is periostin increased or decreased in cAD skin

A

INCREASED (more itch!)

EV ACVD Study (52 decks)

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