PMID- 24466057
OWN - NLM
STAT- MEDLINE
DCOM- 20140915
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 1
DP  - 2014
TI  - Calcitonin gene-related peptide regulates type IV hypersensitivity through 
      dendritic cell functions.
PG  - e86367
LID - 10.1371/journal.pone.0086367 [doi]
LID - e86367
AB  - Dendritic cells (DCs) play essential roles in both innate and adaptive immune 
      responses. In addition, mutual regulation of the nervous system and immune system 
      is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP), is 
      a potent regulator in immune responses; in particular, it has anti-inflammatory 
      effects in innate immunity. For instance, a deficiency of the CGRP receptor 
      component RAMP 1 (receptor activity-modifying protein 1) results in higher 
      cytokine production in response to LPS (lipopolysaccharide). On the other hand, 
      how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we 
      show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 
      production in DCs using an in vitro co-culture system and an in vivo 
      ovalbumin-induced delayed-type hypersensitivity (DTH) model. CGRP also 
      down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 
      and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+) DCs in 
      draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. 
      Moreover, these CCR2(+) DCs highly expressed IL-12 and CD80, resulting in more 
      effective induction of Th1 differentiation compared with CCR2(-) DCs. These 
      results indicate that CGRP regulates Th1 type reactions by regulating expression 
      of cytokines, chemokines, and chemokine receptors in DCs.
FAU - Mikami, Norihisa
AU  - Mikami N
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Sueda, Kaori
AU  - Sueda K
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Ogitani, Yusuke
AU  - Ogitani Y
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Otani, Ippei
AU  - Otani I
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Takatsuji, Miku
AU  - Takatsuji M
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Wada, Yasuko
AU  - Wada Y
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Watanabe, Keiko
AU  - Watanabe K
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Yoshikawa, Rintaro
AU  - Yoshikawa R
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Nishioka, Satoshi
AU  - Nishioka S
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Hashimoto, Nagisa
AU  - Hashimoto N
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Miyagi, Yayoi
AU  - Miyagi Y
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Fukada, So-ichiro
AU  - Fukada S
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Yamamoto, Hiroshi
AU  - Yamamoto H
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
FAU - Tsujikawa, Kazutake
AU  - Tsujikawa K
AD  - Laboratory of Molecular and Cellular Physiology, Graduate School of 
      Pharmaceutical Sciences, Osaka University, Osaka, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140121
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (B7-1 Antigen)
RN  - 0 (Ccl12 protein, mouse)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Ccr2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Monocyte Chemoattractant Proteins)
RN  - 0 (Ramp1 protein, mouse)
RN  - 0 (Receptor Activity-Modifying Protein 1)
RN  - 0 (Receptors, CCR2)
RN  - 187348-17-0 (Interleukin-12)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
SB  - IM
MH  - Animals
MH  - B7-1 Antigen/immunology
MH  - Calcitonin Gene-Related Peptide/*immunology
MH  - Cell Differentiation/immunology
MH  - Chemokine CCL2/immunology
MH  - Dendritic Cells/*immunology
MH  - Down-Regulation/immunology
MH  - Hypersensitivity, Delayed/*immunology
MH  - Interleukin-12/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Monocyte Chemoattractant Proteins/immunology
MH  - Receptor Activity-Modifying Protein 1/immunology
MH  - Receptors, CCR2/immunology
MH  - Th1 Cells/immunology
PMC - PMC3897726
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/01/28 06:00
MHDA- 2014/09/16 06:00
PMCR- 2014/01/21
CRDT- 2014/01/28 06:00
PHST- 2013/10/01 00:00 [received]
PHST- 2013/12/06 00:00 [accepted]
PHST- 2014/01/28 06:00 [entrez]
PHST- 2014/01/28 06:00 [pubmed]
PHST- 2014/09/16 06:00 [medline]
PHST- 2014/01/21 00:00 [pmc-release]
AID - PONE-D-13-40152 [pii]
AID - 10.1371/journal.pone.0086367 [doi]
PST - epublish
SO  - PLoS One. 2014 Jan 21;9(1):e86367. doi: 10.1371/journal.pone.0086367. eCollection 
      2014.