Differential regulation and impact of fucosyltransferase VII and core 2 β1,6‐ N ‐acetyl‐glycosaminyltransferase for generation of E ‐selectin and P ‐selectin ligands in murine CD 4 + T cells

• Published in: Immunology Vol. 137; no. 4; pp. 294 - 304
• Main Authors: Schroeter, Micha F., Ratsch, Boris A., Lehmann, Jeanette, Baumgrass, Ria, Hamann, Alf, Syrbe, Uta
• Format: Journal Article
• Language: English
• Published: 01-12-2012
• ISSN: 0019-2805; 1365-2567
• DOI: 10.1111/imm.12011

Ligands for
E
‐selectin and
P
‐selectin (
E
‐lig and
P
‐lig) are induced on
CD
4
+
T cells upon differentiation into effector
T
cells. Glycosyltransferases, especially α 1,3‐fucosyltransferase VII (
F
uc
T
‐VII) and core 2 β1,6‐
N
‐acetyl‐glycosaminyltransferase I (
C
2
G
lc
NA
c
T
‐I), are critical for their synthesis. We here analysed the signals that control the expression of
E
‐lig,
P
‐lig and m
RNA
coding for
F
uc
T
‐VII and
C
2
G
lc
NA
c
T
‐I. In line with previous reports, we found that P‐lig expression correlates with the regulation of
C
2
G
lc
NA
c
T
‐I, whereas
E
‐lig expression can occur at low levels of
C
2
G
lc
NA
c
T
‐I m
RNA
but requires high
F
uc
T
‐VII m
RNA
expression. Interestingly, the two enzymes are regulated by different signals. Activation‐induced
C
2
G
lc
NA
c
T
‐I up‐regulation under permissive (T helper type 1) conditions was strongly reduced by cyclosporin
A
(
C
s
A
), suggesting the involvement of
T
‐cell receptor‐dependent, calcineurin/
NFAT
‐dependent signals in combination with interleukin‐12 (
IL
‐12) ‐mediated signals in the regulation of
C
2
G
lc
NA
c
T
‐I. In contrast, expression of
F
uc
T
‐VII m
RNA
was not significantly inhibited by
C
s
A
. Interleukin‐4 inhibited the expression of
F
uc
T
‐VII but
IL
‐2 and
IL
‐7 were found to support induction of
F
uc
T
‐VII and
E
‐lig.
E
‐selectin,
P
‐selectin and their ligands initially appeared to have rather overlapping functions. These findings however, unravel striking differences in the regulation of
E
‐lig and
P
‐lig expression, dictated by the dominance of
F
uc
T
‐VII and
C
2
G
lc
NA
c
T
‐I, respectively, and their dependency on signals from either promiscuous or homeostatic cytokines (
F
uc
T
‐VII) or a strong
T
‐cell receptor signal in combination with inflammatory cytokines in case of
C
2
G
lc
NA
c
T
‐I.