TSH-receptor-expressing fibrocytes and thyroid-associated ophthalmopathy
#MMPMID25560705
Smith TJ
Nat Rev Endocrinol
2015[Mar]; 11
(3
): 171-81
PMID25560705
show ga
Thyroid-associated ophthalmopathy (TAO) is a vexing and undertreated ocular
component of Graves disease in which orbital tissues undergo extensive
remodelling. My colleagues and I have introduced the concept that fibrocytes
expressing the haematopoietic cell antigen CD34 (CD34(+) fibrocytes), which are
precursor cells of bone-marrow-derived monocyte lineage, express the TSH receptor
(TSHR). These cells also produce several other proteins whose expression was
traditionally thought to be restricted to the thyroid gland. TSHR-expressing
fibrocytes in which the receptor is activated by its ligand generate extremely
high levels of several inflammatory cytokines. Acting in concert with TSHR, the
insulin-like growth factor 1 receptor (IGF-1R) expressed by orbital fibroblasts
and fibrocytes seems to be necessary for TSHR-dependent cytokine production, as
anti-IGF-1R blocking antibodies attenuate these proinflammatory actions of TSH.
Furthermore, circulating fibrocytes are highly abundant in patients with TAO and
seem to infiltrate orbital connective tissues, where they might transition to
CD34(+) fibroblasts. My research group has postulated that the infiltration of
fibrocytes into the orbit, their unique biosynthetic repertoire and their
proinflammatory and profibrotic phenotype account for the characteristic
properties exhibited by orbital connective tissues that underlie susceptibility
to TAO. These insights, which have emerged in the past few years, might be of use
in therapeutically targeting pathogenic orbit-infiltrating fibrocytes selectively
by utilizing novel biologic agents that interfere with TSHR and IGF-1R
signalling.
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