Biology Reference
In-Depth Information
Table 17.1 Chemokine Superfamily—cont'd
Mouse Ligand and
Alternate Names
Chemokine
Human Ligand and Alternate Names
Receptor
CXCL9
Mig
Mig
CXCR3
CXCL10
IP-10
CRG-2, IP-10
CXCR3
CXCL11
I-TAC
I-TAC
CXCR3
CXCL12
SDF-1
α
, SDF-1
β
, PBSF
SDF-1
α
, SDF-1
β
CXCR4
CXCL13
BCA-1, BLC
BLC
CXCR5
CXCL14
BRAK, BMAC
BRAK, BMAC
Unknown
CXCL15
Lungkine
Unknown
CXCL16
CXCL16
CXCL16
CXCR6
CX
3
C family
CX
3
CL1
Fractalkine, ABCD-3
Neurotactin
CX3CR1
(MCP-1, or monocyte chemoattractant protein-1), CCL3 (MIP-1α, or mac-
rophage inflammatory protein-1α), CCL5 (RANTES, or regulated on acti-
vation normal T cell expressed and secreted), CXCL9 (Mig, or monokine
induced by IFN-γ), CXCL10 (IP-10, or IFN-γ-inducible protein-10), CXCL11
(I-TAC, or IFN-inducible T-cell α chemoattractant), and CXCL2 (MIP-2) and
are induced to high levels of expression by inflammatory stimuli such as
LPS, IL-1, IFN-γ, and TNF-α
[4]
. The corresponding inflammatory chemo-
kine receptors include CCR1, CCR2, CCR5, CXCR3, and CXCR2. Generally,
these receptors have more redundant ligand-binding interactions com-
pared to “homeostatic” receptors and tend to be expressed on cells with
an “effector” phenotype. Although simplistic, the functional division pro-
vides insight into how specific chemokine interactions orchestrate leuko-
cyte movements during development, how they orchestrate antigen-driven
differentiation and migration to sites of inflammation, and how they ulti-
mately contribute to disease
[17]
. By contrast, “constitutive” or “homeo-
static” chemokines are produced in discrete amounts within lymphoid and
nonlymphoid tissues and are responsible for physiologic leukocyte migra-
tion during immune surveillance, antigen sampling, and formation of the
architectural framework of secondary lymphoid organs
[16]
. Homeostatic
chemokine receptor:ligand pairs include but are not limited to CCR7:CCL19
(ELC) and CCL21 (SLC, or secondary lymphoid tissue chemokine),
CCR9:CCL25 (TECK, or thymus-expressed ligand), CCR10:CCL27 (CTACK,
or cutaneous T-cell-attracting chemokine), and CXCR4:CXCL12 (SDF-1).
399
To date, the study of chemokine biology has largely focused on the corre-
lation of protein or mRNA levels with a functional event, the administra-
tion of neutralizing antibodies
in vivo
and
in vitro,
or the use of genetically
modified mice that lack (or overexpress) a particular chemokine or recep-
tor. A significant amount of experimental data exploring the role of chemo-
kines during inflammation was initially generated using either solid organ
transplantation (skin, trachea, and cardiac) or infectious disease models.
Fortunately, an emerging body of work has also defined the evolution of
chemokine cascades following allogeneic HCT (
Figure 17.1
), and these
studies are discussed in detail below.
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