Research Article
Terminally Differentiated Epithelial Cells of the Thymic Medulla
and Skin Express Nicotinic Acetylcholine Receptor Subunit 3
Aichurek Soultanova, Alexandra R. Panneck, Amir Rafiq, and Wolfgang Kummer
Institute of Anatomy and Cell Biology, German Center for Lung Research, Justus-Liebig-University Giessen, Aulweg 123,
35385 Giessen, Germany
Correspondence should be addressed to Wolfgang Kummer; wolfgang.kummer@anatomie.med.uni-giessen.de
Received 22 April 2014; Accepted 13 June 2014; Published 3 July 2014
Academic Editor: Koichiro Kawashima
Copyright © 2014 Aichurek Soultanova et al. his is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
In the thymus, T cell maturation is inluenced by cholinergic signaling, and the predominantly expressed receptor is the 3-
subunit of nicotinic acetylcholine receptors, encoded by the chrna3 gene. We here determined its cellular distribution utilizing
an appropriate eGFP-expressing reporter mouse strain. Neither T cells (CD4, CD8) nor mesenchymal cells (desmin-positive)
expressed eGFP. In the thymic medulla, eGFP-positive cells either were scattered or, more frequently, formed small clusters
resembling Hassall’s corpuscles. Immunolabeling revealed that these cells were indeed terminally diferentiated epithelial cells
expressing keratin 10 (K10) but neither typical cortical (K8, K18) nor medullary keratins (K5, K14). hese labeling patterns relected
those in the epidermis of the skin, where overlap of K10 and eGFP expression was seen in the stratum granulosum, whereas
underlying basal cells displayed K5-immunoreactivity. A substantial portion of thymic eGFP-positive cells was also immunoreactive
to chromogranin A, a peptide previously reported in epidermal keratinocytes in the stratum granulosum. Its fragment catestatin
has multiple biological activities, including suppression of proinlammatory cytokine release from macrophages and inhibition
of 34 nAChR. he present indings suggest that its thymic production and/or release are under cholinergic control involving
nAChR containing the 3-subunit.
1. Introduction
he thymus is the site of step-wise maturation of na¨ ıve T
cells from immature thymocytes which occurs along with
positive and negative selection processes while thymocytes
migrate from the cortex to the medulla. hese processes are
inluenced by cholinergic signaling [1–4], and acetylcholine
(ACh) is endogenously synthesized in the thymus [5–7].
Signaling via nicotinic ACh receptors (nAChR) has
received particular attention. hese receptors are pentamers
composed of various subunit combinations. he “muscle
type” nAChR originally identiied at the motor endplate
consists of two 1-, one 1-, one - (or - at fetal stage),
and one -subunit, and these are also expressed by myoid
[8, 9] and epithelial cells of the thymic medulla [10–13].
hymic expression and presentation of muscle-type nAChR
subunits have been associated with a frequent (85%) variant
of myasthenia gravis, a disease of the motor endplate, where
autoantibodies against such subunits are formed, as the thy-
mus frequently shows abnormal structure in this condition
and thymectomy is beneicial for the patients [14].
“Neuronal” nAChR are homo- or heteromers of -
subunits 2–7 and 9-10 (8 is expressed only in chicken) and
-subunits 2–4 [15–17]. Despite their designation as “neu-
ronal” they are widely expressed outside the nervous system
including the thymus [18, 19]. Amongst them, subunits 3,
5, and 4 exhibit highest expression in early postnatal
mouse thymus, reaching 7–15% of mRNA content found
in brain as standard [19]. heir genes—chrna3, chrna5, and
chrnb4—are clustered on chromosome 9 in mice, and, when
coexpressed, the translated proteins assemble to functional
3(5)4 nAChR with either 2 - and 3 -subunit or 3 -
and 2 -subunit chains [15, 20]. he 3-subunit is essential
for receptor function and may occur with or without an
additional 5-subunit in these receptors while the 5-subunit
Hindawi Publishing Corporation
BioMed Research International
Volume 2014, Article ID 757502, 9 pages
http://dx.doi.org/10.1155/2014/757502