Immune checkpoints inT cell-mediated tissue inflammation
Miyuki Azuma
P「ofesso「 ofMolecula「Immunology atTMDU

Q 翌ば悶

t hens e
�;� �specific immune checkp oints.
P lease exp lain what this is.
lo；悶。 ：宅ば悶

A: Immune checkpoints help to 「egulate theimmune system. This is important to p「eventch「onic inflammation, in helping to avoid
excessive damage to the a「ea su「「oundingthe affected tissue.

Q □'塁。（閃守ば悶はご悶。悶

faces of othe「O「gans,showed stable ex­

but not othe「 0「al mucosae o「 mucosal su「­invading pathogens o「 tumo「s. This 「egula­tion is achieved by 「equi「ing a second signal

A: Masticato「y mucosae (the laye「s of tissuesfo「 full immune system activation,o「 by in­cove「ing the gums,top of the tongue,and

when the immune system e「「oneously at­tacks the body's own healthy cells instead ofhibiting activity because the ta「get is 「ecog­

ha「d portion of the 「oof of the mouth) a「enized as a no「mal part of the body. In cance「,specialized o「al mucosae fa「 masticationimmune checkpoints a「e often manipulated(c「ushing and digesting foods), as well as

to supp「ess anti-tumo「 immune 「esponses,P「otection f「om envi「onmental damage.

allowing the tumo「 to g「ow in an un「est「ict­Ou「 initial inte「est in masticato「y mucosae

ed manne「. Additionally, immune check­a「ose f「om histological studies of tissues

points can also be impo「tant in cases ofand cells exp「essing B7-Hl (also known as

B7-Hl (PD-Ll), a ligand of immune checkpoint 『ecepto『PD-1 exp『essedon masticato『ymucosae, negatively『egulates T cell-mediated tissue
inflammation
A. Selective exp 『ession of B7-Hl
on masticato 『ymucosae
Dorsal tongue

f0「PD-1,an important inhibito「y 「ecepto「 inT cells. We found that masticato「y mucosae,cu les on masticato ry muco sae inthe m outh. What made yo u focus
on this pr ocess, and what did yo u
disc over?

the development of autoimmunity,which isPD-Ll),which is a ligand (binding partne「)B. Blockade of B7-Hl enhances
CD4 • T-cell infilt 『ationDorsal tongueanti-B7-Hl mAb
ControlGingiva

P「ession of B7-Hl.

Q 芯〗 r：ば゜u「g閉悶はごば悶翌益

your investigation of immunity inmasticato y mucosae. Can you「exp lain what aspect of the im­mune resp onse was discoveredby using this technique in masti­
cato ry muco sae?

A: We knew that B7-Hl exp「essed on anti­
gen-p「esenting cells o「 tumo「 cells could in­te「act withPD-1 and inhibitT-cell activation,and that the p「esence of B7-Hl in tissues
could 「egulate the activation ofT cells. How­eve「,we did not know how B7-Hl exp「es­sion was 「egulated in o「al mucosae o「 howB7-Hl functioned in the o「al cavity. The o「almucosae 「eceive external stimuli th「oughthe mucosal surface and internal stimuli
th「ough immune cells,such as infilt「ating Tcells and mac「ophages. Antigen stimulation
studies,combined with the use of unique

H&E

TCR-t「ansgenic mice, allowed us to dete「­mine how B7-Hl functions: We learned thatヽ ー・・...,..
.
、 、.
9「ぃニke「atinocyte/epithelial cell-associated B7-99Ventral tongue

Hl inte「acts with PD-1 that is exp「essed onBuccal mucosa

antigen-p「imed, tissue-infilt「ating CD4• TCD4,,.
t，：：・：·•`•，- ．
ヽ―ふ•;, .. 'f .
»·• : ;、二II；ふI ・ ．． ,. ．.
IScale ba「S= SOµm.••：

cells to p「ovide negative 「egulato「y signals.
會―,--Antigen-specific CD4 + T cells we「e t「ansfe「「ed to B7-Hl/
PD-1-double knockout bone ma「「ow chime「a mice[Reprinted with pe「missionf「om Mucosa/ lmmunol., doi:10.1038/mi.2016.89]

Dr. Azuma completed dental and g「aduate school at TMDU, whe「e she 「eceived he「DDS and PhD. She pe「fa「med postdocto「al 「esea「ch in the Depa「tment of Immunology atDNAX Resea「ch Institute in Palo Alto, CA, USA and continued he「 ca「ee「 as an AssistantP「ofesso「 of Immunology at」untendo Unive「sity School of Medicine, and as a Resea「chAssociate in the Depa「tment of Immunology at National Child「en'sMedical Res ea「ch Cente「in Tokyo. She 「etu「ned to TMDU as a P「ofesso「ofMolecula「|mmunology in 2000

Q 塁？。 悶儡は翌tu

ica l imp lications

A: The induction of B7-Hl exp「ess1on 1nmasticato「y mucosae appea「s to be impo「­tant in the p「evention of excess immune 「e­sponses in ch「onically inflamed tissue and inhomeostasis in the mouth.

Mucosa/ lmmunol., doi:10.1038/mi.2016.89