The Immune Inhibitory Receptor LAIR-1 Is Highly Expressed by Plasmacytoid Dendritic Cells and Acts Complementary with NKp44 to Control IFNα Production

被引:71
作者
Bonaccorsi, Irene [1 ]
Cantoni, Claudia [2 ,3 ,4 ]
Carrega, Paolo [4 ]
Oliveri, Daniela [1 ]
Lui, Gabrielle [4 ]
Conte, Romana [5 ]
Navarra, Michele [6 ]
Cavaliere, Riccardo [1 ]
Traggiai, Elisabetta [4 ,7 ]
Gattorno, Marco [4 ,7 ]
Martini, Alberto [4 ,7 ]
Mingari, Maria Cristina [2 ,5 ]
Moretta, Alessandro [2 ,3 ]
Ferlazzo, Guido [1 ]
机构
[1] Univ Messina, Dept Human Pathol, Lab Immunol & Biotherapy, Messina, Italy
[2] Univ Genoa, Dept Expt Med DIMES, Genoa, Italy
[3] Univ Genoa, CERB, Genoa, Italy
[4] Ist Giannina Gaslini, I-16148 Genoa, Italy
[5] Ist Nazl Ric Canc, I-16132 Genoa, Italy
[6] Univ Messina, Pharmaco Biol Dept, Messina, Italy
[7] Univ Genoa, Dept Pediat, Genoa, Italy
关键词
SYSTEMIC-LUPUS-ERYTHEMATOSUS; NATURAL-KILLER-CELLS; IMMUNOGLOBULIN SUPERFAMILY; AUTOIMMUNE-DISEASES; I INTERFERONS; T-CELLS; DIFFERENTIATION; ACTIVATION; LYMPHOCYTES; PRECURSORS;
D O I
10.1371/journal.pone.0015080
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells endowed with the capacity of producing large amounts of IFN alpha. Here we show that the Leukocyte-Associated Ig-like Receptor-1 (LAIR-1) is abundantly expressed on pDCs (the highest expression among all leukocytes) and its cross-linking inhibits IFNa production in response to Toll-like receptor ligands. Remarkably, LAIR-1 expression in pDCs is down-regulated in the presence of interleukin (IL)-3, thus indicating coordinated functions with NKp44, another pDC inhibitory receptor, which is conversely induced by IL-3. Nevertheless, the expression of NKp44 in pDCs isolated from secondary lymphoid organs, which is thought to be influenced by IL-3, is not coupled to a decreased expression of LAIR-1. Interestingly, pDCs isolated from peripheral blood of systemic lupus erithematosus (SLE) patients express lower levels of LAIR-1 while displaying slight but consistent expression of NKp44, usually undetectable on pDCs derived from healthy donors. Using sera derived from SLE patients, we show that LAIR-1 and NKp44 display synergistic inhibitory effects on IFNa production by interleukin IL-3 cultured pDCs stimulated with DNA immunocomplexes. In conclusion, our results indicate that the inhibitory function of LAIR-1 may play a relevant role in the mechanisms controlling IFNa production by pDCs both in normal and pathological innate immune responses.
引用
收藏
页数:8
相关论文
共 37 条
[1]   Chemerin expression marks early psoriatic skin lesions and correlates with plasmacytoid dendritic cell recruitment [J].
Albanesi, Cristina ;
Scarponi, Claudia ;
Pallotta, Sabatino ;
Daniele, Roberta ;
Bosisio, Daniela ;
Madonna, Stefania ;
Fortugno, Paola ;
Gonzalvo-Feo, Safiye ;
Franssen, Jean-Denis ;
Parmentier, Marc ;
De Pita, Ornella ;
Girolomoni, Giampiero ;
Sozzani, Silvano .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (01) :249-258
[2]   Type I interferon in systemic lupus erythematosus and other autoimmune diseases [J].
Banchereau, Jacques ;
Pascual, Virginia .
IMMUNITY, 2006, 25 (03) :383-392
[3]   FcγRIIa is expressed on natural IFN-α-producing cells (plasmacytoid dendritic cells) and is required for the IFN-α production induced by apoptotic cells combined with lupus IgG [J].
Båve, U ;
Magnusson, M ;
Eloranta, ML ;
Perers, A ;
Alm, GV ;
Rönnblom, L .
JOURNAL OF IMMUNOLOGY, 2003, 171 (06) :3296-3302
[4]   The combination of apoptotic U937 cells and lupus IgG is a potent IFN-α inducer [J].
Båve, U ;
Alm, GV ;
Rönnblom, L .
JOURNAL OF IMMUNOLOGY, 2000, 165 (06) :3519-3526
[5]   Induction of dendritic cell differentiation by IFN-α in systemic lupus erythematosus [J].
Blanco, P ;
Palucka, AK ;
Gill, M ;
Pascual, V ;
Banchereau, J .
SCIENCE, 2001, 294 (5546) :1540-1543
[6]   Siglec-H is an IPC-specific receptor that modulates type IIFN secretion through DAP12 [J].
Blasius, AL ;
Cella, M ;
Maldonado, J ;
Takai, T ;
Colonna, M .
BLOOD, 2006, 107 (06) :2474-2476
[7]   NKP44 triggers NK cell activation through DAP12 association that is not influenced by a putative cytoplasmic inhibitory sequence [J].
Campbell, KS ;
Yusa, S ;
Kikuchi-Maki, A ;
Catina, TL .
JOURNAL OF IMMUNOLOGY, 2004, 172 (02) :899-906
[8]  
Cantoni C, 1999, EUR J IMMUNOL, V29, P3148, DOI 10.1002/(SICI)1521-4141(199910)29:10<3148::AID-IMMU3148>3.0.CO
[9]  
2-L
[10]   NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily [J].
Cantoni, C ;
Bottino, C ;
Vitale, M ;
Pessino, A ;
Augugliaro, R ;
Malaspina, A ;
Parolini, S ;
Moretta, L ;
Moretta, A ;
Biassoni, R .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (05) :787-795