Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 135

Table 3.32. FoxP3 and T Reg -cell markers (Source: [ 244 ]; CCR: CC-chemokine receptor; CTLA:
cytotoxic T-lymphocyte antigen; GARP, glycoprotein-A repetition predominant protein; GITR,
glucocorticoid-induced TNFR-related protein, or TNFRSF18; ICOS, inducible T-cell costimulator
[CD278]; IL, interleukin; LAP: latency-associated peptide (region of TGF precursor); MS4a4b:

membrane-spanning 4-domain, subfamily A, member 4B; PdCD: programmed cell death). Short
aliases CD i are suitable for small-sized tables, but do not display their function. CD25 corresponds
to low-affinity receptor IL2R

β

; CD27 to tumor-necrosis factor receptor superfamily member TN-
FRSF7; CD31 to PECAM1; CD39 to ectonucleoside triphosphate diphosphohydrolase ENTPD1;
CD45 to PTPRc phosphatase; CD62L to L-selectin; CD69 to C-type lectin domain family member
CLec2c; CD73 to ecto 5 -nucleotidase; CD95 TNFRSF6a; CD103 to

α

α E -integrin; and CD304 to

neuropilin-1.

Activation Homing Effector Cell fate

FoxP3 CD45 CD31/62L/103/304, CD39/73 CD6/27/95

CD25/69, CCR4/6/9 CD2/80/86, IL1R

HLADR IL10/17, GARP, GITR

Granzyme-B, MS4a4b,

Galectin-1/10 Galectin-3

LAP, TNFSF11, PdCD1, TNFRSF4

ICOS, CTLA4

The main isoform FoxP3b lacks the Leu-X-X-Leu-Leu motif encoded by
exon 2 that serves to bind to retinoic acid receptor-related orphan receptor- as

well as N-terminal residues that may mediate the interaction with nuclear factor of
activated T cells [ 244 ].
The regulator of cytokine signaling, SUMo (small ubiquitin-related modi-
fier) ligase PIAS1 (protein inhibitor of activated signal transducer and activator
of transcription STAT1), represses FoxP3 expression by epigenetic inhibition,
i.e., maintaining a repressive chromatin state of the FOXP3 promoter [ 248 ].
Ligase PIAS1 recruits methyltransferases, thereby promoting the methylation of the
FOXP3 promoter. Enzyme PIAS1 also selectively blocks the binding of NF

γ

Band
STAT1 to gene promoters [ 249 ]. Recruitment of PIAS1 to chromatin requires its
phosphorylation (Ser90) upon various immune regulatory stimuli, such as tumor-
necrosis factor and activated T-cell receptor. Inhibitor of NF

κ

κ B kinase- α , but not

IKK β , phosphorylates PIAS1 [ 249 ].

Role in Antiviral Immunity

Regulatory T cells promote early antiviral immune response at a site of infection
[ 250 ]. Regulatory T cells accumulate, are activated, and proliferate both at the
infection site and in draining lymph nodes.
Transcription factor FoxP3, transforming growth factor- (particularly activated

by integrins of dendritic cells), and IL2 support a T Reg cell type.
The presence of regulatory T cells in the lymph node prevents influx and
activation of effector T cells, natural killer cells, and dendritic cells that thus migrate
into the site of viral infection.

β