Dendritic cells: a family portrait at mid-gestation.
Recent advances in our understanding of dendritic cells (DCs) and their role in tolerance and immunity has fuelled study of their normal development and function within the reproductive tract. The common hypothesis that pregnancy is a state of immune suppression or deviation now includes the idea that alterations in DC phenotype and function are critical for maternal tolerance. We chose to study DCs in the uterus and lymphoid tissue in non-pregnant and pregnant mice at mid-gestation to understand what DC-related factors may be involved in premature birth. We used a mouse model where the mother's immune system has been shown to respond to the male antigen H-Y. Observed differences among DCs in the uterus, uterine draining nodes and spleen, even in non-pregnant mice, suggest the existence of a specialized uterus-specific subset of DCs. We further found that, amongst CD45(+) CD11c(+) cells in the uterus and peripheral lymphoid tissue of pregnant mice, expression of major histocompatibility complex class II (MHC II) and costimulatory molecules (i.e. CD80) was similar to that in the non-pregnant state. Moreover, there was no pregnancy-related decrease in the proportion of CD11c(+) cells in the uterus or in the uterine node that were CD11b(-) CD8(+). Pregnancy increased the CD11b(+) subsets and the expression of chemokine (C-C motif) ligand 6 (CCL6) in DCs of the uterine draining nodes. Finally, DC subsets showed variable expression, with respect to tissue and pregnancy, of the cytokine interleukin-15, which is important in lymphoid cell homeostasis. For DCs, pregnancy is not a state of immune paralysis, but of dynamic developmental change.
Bizargity
Peyman
P
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA.
Bonney
Elizabeth A
EA
D000818:Animals; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005865:Gestational Age; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007108:Immune Tolerance / Q000276:immunology; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D019409:Interleukin-15 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000032:analysis; D008198:Lymph Nodes / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014599:Uterus / Q000276:immunology*
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D019409:Interleukin-15; D017493:Leukocyte Common Antigens
Nat Immunol. 2004 Mar;5(3):266-71
14758358
Am J Pathol. 2003 Mar;162(3):887-96
12598322
Nature. 1995 Aug 24;376(6542):695-8
7544442
J Exp Med. 2002 Nov 18;196(10):1307-19
12438422
J Immunol. 2004 May 15;172(10):5893-9
15128769
Circ Res. 2000 Sep 15;87(6):448-52
10988235
Am J Obstet Gynecol. 1994 Sep;171(3):805-11
8092233
Blood. 2003 Sep 15;102(6):2187-94
12791652
Immunology. 2001 Jul;103(3):382-9
11454068
Clin Exp Immunol. 1973 Jan;13(1):107-24
4764346
Mt Sinai J Med. 2001 May;68(3):160-6
11373688
J Immunol. 2007 Oct 15;179(8):5474-82
17911634
Blood. 2002 Mar 15;99(6):2084-93
11877283
J Immunol. 2003 Sep 15;171(6):2937-44
12960317
Nat Immunol. 2007 Jan;8(1):11-3
17179963
Nat Immunol. 2006 Jun;7(6):663-71
16680143
Science. 1992 Nov 13;258(5085):1156-9
1439825
Cell. 1992 Dec 24;71(7):1065-8
1335362
J Clin Invest. 2007 May;117(5):1399-411
17446933
Exp Cell Res. 2006 May 1;312(8):1312-22
16455075
Am J Reprod Immunol. 2008 Feb;59(2):167-81
18211542
Nat Med. 2007 Dec;13(12):1450-7
18026113
J Immunol. 1997 Jan 1;158(1):40-7
8977173
J Immunol. 2007 Oct 1;179(7):4383-9
17878333
Biol Reprod. 2004 Apr;70(4):1018-23
14681197
Am J Reprod Immunol. 2004 Apr;51(4):275-82
15212680
Eur J Immunol. 2006 Jan;36(1):82-94
16358362
Allergol Int. 2007 Sep;56(3):183-91
17646733
J Clin Invest. 2007 Sep;117(9):2570-82
17710230
Am J Pathol. 2000 Jul;157(1):159-69
10880386
Placenta. 2008 Apr;29(4):317-23
18289671
J Invest Dermatol. 1999 Dec;113(6):991-8
10594742
J Exp Med. 1985 Mar 1;161(3):526-46
3871837
Cell Immunol. 1988 Sep;115(2):471-80
3409331
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):8981-6
15184678
J Immunol. 2005 Apr 15;174(8):4657-61
15814689
J Immunol. 1997 Aug 15;159(4):1993-2000
9257866
Eur J Obstet Gynecol Reprod Biol. 2003 Sep 22;110 Suppl 1:S19-27
12965087
J Immunol. 2003 Dec 15;171(12):6742-9
14662878
Reprod Sci. 2007 Sep;14(6):548-59
17959883
Clin Immunol. 2008 Jan;126(1):104-17
17974483
Blood. 2001 Sep 1;98(5):1512-23
11520802
Curr Biol. 1996 May 1;6(5):519-22
8805259
Immunol Invest. 2004;33(4):385-95
15624697
Nat Rev Immunol. 2007 Jan;7(1):19-30
17170756
J Exp Med. 1998 Jul 20;188(2):373-86
9670049
Blood. 2003 Jul 1;102(1):388-93
12649154
J Reprod Immunol. 2007 Dec;76(1-2):68-74
17482268
Annu Rev Immunol. 1997;15:39-61
9143681
Reproduction. 2007 Jan;133(1):275-83
17244753
Science. 1998 Aug 21;281(5380):1191-3
9712583
Am J Obstet Gynecol. 2000 Feb;182(2):351-7
10694336
J Immunol. 2000 Mar 15;164(6):2978-86
10706685
J Exp Med. 2002 May 20;195(10):1257-66
12021306
J Exp Med. 2000 Jul 17;192(2):259-70
10899912
Biol Reprod. 2002 Jun;66(6):1853-61
12021072
Nat Rev Immunol. 2004 Jun;4(6):469-78
15173835