PMID- 36047204
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220909
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 45
IP  - 9
DP  - 2022
TI  - TARC/CCL17 Expression Is Associated with CD8(+) T Cell Recruitment in 
      Abacavir-Induced Skin Hypersensitivity in HLA-Transgenic Mice.
PG  - 1347-1353
LID - 10.1248/bpb.b22-00313 [doi]
AB  - Abacavir (ABC)-induced hypersensitivity (AHS) is strongly associated with human 
      leukocyte antigen (HLA)-B*57 : 01 expression. Previous studies have demonstrated 
      the feasibility of applying the HLA-transgenic mouse model in this context. 
      ABC-induced adverse reactions were observed in HLA-B*57 : 01 transgenic 
      (B*57 : 01-Tg) mice. Moreover, regulating immune tolerance could result in severe 
      AHS that mimics symptoms observed in the clinical setting, which were modeled in 
      CD4(+) T cell-depleted programmed death-1 receptor (PD-1) knockout B*57 : 01-Tg 
      (B*57 : 01-Tg/PD-1(-/-)) mice. Here, we aimed to examine whether thymus and 
      activation-regulated chemokine (TARC)/CCL17 level can be used as a biomarker for 
      AHS. Serum TARC levels increased in HLA-B*57 : 01-transgenic mice following oral 
      administration of ABC; this increase was associated with the severity of skin 
      toxicity. In ABC-fed CD4(+) T cell-depleted B*57 : 01-Tg/PD-1(-/-) mice, TARC was 
      detected in the epidermal keratinocytes of the ear. Skin toxicity was 
      characterized by the infiltration of CD8(+) T cells partially expressing C-C 
      chemokine receptor type 4, which is the primary receptor for TARC. In vivo TARC 
      neutralization effectively alleviated the symptoms of ear skin redness and blood 
      vessel dilatation. Moreover, TARC neutralization suppressed the infiltration of 
      CD8(+) T cells to the ear skin but did not affect the ABC-induced adaptive immune 
      response. Therefore, TARC was involved in ABC-induced skin toxicity and 
      contributed to the recruitment of CD8(+) T cells to skin. This evidence suggests 
      that serum TARC level may be a functional biomarker for AHS.
FAU - Gao, Yuying
AU  - Gao Y
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Kuwahara, Saki
AU  - Kuwahara S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Kazaoka, Akira
AU  - Kazaoka A
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Ito, Kousei
AU  - Ito K
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
FAU - Aoki, Shigeki
AU  - Aoki S
AD  - Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba 
      University.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Ccl17 protein, mouse)
RN  - 0 (Chemokine CCL17)
RN  - 0 (Chemokines)
RN  - 0 (Cyclopropanes)
RN  - 0 (HLA-B Antigens)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 4Q86AH641A (Dideoxyadenosine)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Animals
MH  - *CD8-Positive T-Lymphocytes/immunology
MH  - *Chemokine CCL17/genetics
MH  - Chemokines
MH  - Cyclopropanes/adverse effects
MH  - *Dermatitis, Atopic
MH  - Dideoxyadenosine/adverse effects/analogs & derivatives
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Programmed Cell Death 1 Receptor
OTO - NOTNLM
OT  - abacavir
OT  - human leukocyte antigen
OT  - skin hypersensitivity
OT  - thymus and activation-regulated chemokine
EDAT- 2022/09/02 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/09/01 03:46
PHST- 2022/09/01 03:46 [entrez]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
AID - 10.1248/bpb.b22-00313 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2022;45(9):1347-1353. doi: 10.1248/bpb.b22-00313.