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Hematopoietic Stem cell progenitor (CD34+, CD2+, CD5+, CD7+), Plasticity:…
Hematopoietic Stem cell progenitor (CD34+, CD2+, CD5+, CD7+)
Common lymphoid progenitor (in the bone marrow express CD3 and is Double Negative)
CILP
NKP (TOX, NFL3, ID2,ETS1)
NK cells (T-bet EOMES)
CHILP (GATA3)
ILCP
ILC2 (RORalfa, Bcl1 1B GATA3 GFI1)
ILC3 (RORgammaT, AHR, ID2)
ILC1 (T-bet, NFIL3, RUNX3)
Progenitor expressing CD4+ CD8+ alfa-beta TCR and CD3
CD8+ T-alfabeta cell
Tc9
Tc17
Tc2
Tregs
Tc1
CD4+ T-alfabeta cells
Th9
TF: IRF4 PU.1, Cytokines: IL9
Th17
Receptor: KLRB1 CCR6, TF: RORgammaT, Cytokines: IL17
Th2
Receptor: CCR4 CRTH2, TF: GATA3, Cytokines: IL5 IL4
Th22
Receptors: CCR10, TF: FOXO4, Cytokines: IL-22 AHR
Th1
Main receptor: CXCR3, TF: T-bet, Cytokine: IFN gamma IL2
Tfh
Activate B cells and defence againts extracellular pathogens
Tregs
Receptors: CTL4A IL2Ralfa, TF: FOXP3, Cytokines: IL10
Common myeloid progenitor (express CD38)
GMPD
Macrophages DC progenitor
Monocytes
Common DC progenitor
pDC (plasmacytoid) antiviral immunity and producing IFNs
pre-DC progenitor (immunity for infection)
cDC1 (expressing CD141+, CLEC9A+, producing IL-12p70
cDC2 (expressing CD1c+ producing IL-12p70)
Granulocytes
Plasticity: cells are able to take characteristics of different cell subsets (CD4+ overview)
Naive CD4+ T cells
With weak TCR signal -> Treg
With strong TCR signal -> Th1
To determine which subtype: phenotypic analysis and TCR sequencing
Extracellular influence
Th1
+IL-4
Stop IFN gamma production
Th2
IL-4, +IL2
Th1
IL-12 IFN
Th1 type cytokine producer
TGF beta
Th9
Th17
Losing IL-17 and RORgamma but co-colture with IL-12 IL-13 (STAT pathway)
Th1
Tfh
IL-21+ IL4(or IL-6 TGF beta IL12)
Th1, Th2, Th17 type cytokine producer
Treg
IL-6 IL-1B IL-23
IL-17 production
Intracellular impact
PI3K-AkT-mTOR pathway is fundamental
If AkT control is removed in Treg
Th1 or Th17
Plasticity overview in ILCs
Peripheral blood ILC (+CD127 +CD117) lack CD34+, CRTH2 and NKp44 and low level of RORgamma
ILC2
Producing: IL-4, IL-5, IL-13, TF: GATA3
ILC3
Producing: IL-22 IL-17, TF:RORgamma
ILC1
Producing: IFN gamma, TF: Tbet no EOMES
Similarly to Th they transdifferentiate due to cytokine nevironment
ILC1
IL-4
ILC2
IL-1Beta + IL-23
ILC3
ILC2
IL-1 beta + IL-12
ILC1
IL-1beta IL-23 TGFbeta
ILC3
IL-33 and RA
IL-10+ ILC
Nk cell
TgF beta + IL-12
ILC1
ILC3
IL-4
ILC2
IL-1beta+ IL-12
ILC3
Intracellular activity