Ocular Mucosal CD11b+and CD103+Mouse Dendritic Cells under Normal Conditions and in Allergic Immune Responses

被引:43
作者
Khandelwal, Payal [1 ]
Blanco-Mezquita, Tomas [2 ]
Emami, Parisa [1 ]
Lee, Hyun Soo [1 ]
Reyes, Nancy J. [2 ]
Mathew, Rose [2 ]
Huang, Randy [1 ]
Saban, Daniel R. [2 ,3 ]
机构
[1] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA 02114 USA
[2] Duke Univ, Sch Med, Duke Eye Ctr, Dept Ophthalmol, Durham, NC 27710 USA
[3] Duke Univ, Sch Med, Dept Immunol, Durham, NC USA
关键词
CROSS-PRESENTATION; ANTIGEN; SUBSETS;
D O I
10.1371/journal.pone.0064193
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
Steady state dendritic cells (DC) found in non-lymphoid tissue sites under normal physiologic conditions play a pivotal role in triggering T cell responses upon immune provocation. CD11b+ and CD103+ DC have received considerable attention in this regard. However, still unknown is whether such CD11b+ and CD103+ DC even exist in the ocular mucosa, and if so, what functions they have in shaping immune responses. We herein identified in the ocular mucosa of normal wild-type (WT) and Flt3-/- mice the presence of a CD11b+ DC (i.e., CD11c+ MHCII+ CD11b+ CD103-F4/80+ Sirp-a+). CD103+ DC (i.e. CD11c+ MHCII+ CD11b low CD103+ CD8a+ DEC205+ Langerin+) were also present in WT, but not in Flt3-/- mice. These CD103+ DC expressed high levels of Id2 and Flt3 mRNA; whereas CD11b+ DC expressed high Irf4, Csfr, and Cx3cr1 mRNA. Additionally, the functions of these DC differed in response to allergic immune provocation. This was assessed utilizing a previously validated model, which includes transferring specific populations of exogenous DC into the ocular mucosa of ovalbumin (OVA)/alum-primed mice. Interestingly, in such mice, topical OVA instillation following engraftment of exogenous CD11b+ DC led to dominant allergic T cell responses and clinical signs of ocular allergy relative to those engrafted with CD103+ DC. Thus, although CD11b+ and CD103+ DC are both present in the normal ocular mucosa, the CD11b+ DC subset plays a dominant role in a mouse model of ocular allergy.
引用
收藏
页数:8
相关论文
共 23 条
[1]   Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells [J].
Bedoui, Sammy ;
Whitney, Paul G. ;
Waithman, Jason ;
Eidsmo, Liv ;
Wakim, Linda ;
Caminschi, Irina ;
Allan, Rhys S. ;
Wojtasiak, Magdalena ;
Shortman, Ken ;
Carbone, Francis R. ;
Brooks, Andrew G. ;
Heath, William R. .
NATURE IMMUNOLOGY, 2009, 10 (05) :488-495
[2]   Origin of the Lamina Propria Dendritic Cell Network [J].
Bogunovic, Milena ;
Ginhoux, Florent ;
Helft, Julie ;
Shang, Limin ;
Hashimoto, Daigo ;
Greter, Melanie ;
Liu, Kang ;
Jakubzick, Claudia ;
Ingersoll, Molly A. ;
Leboeuf, Marylene ;
Stanley, E. Richard ;
Nussenzweig, Michel ;
Lira, Sergio A. ;
Randolph, Gwendalyn J. ;
Merad, Miriam .
IMMUNITY, 2009, 31 (03) :513-525
[3]   Viral-induced encephalitis initiates distinct and functional CD103+ CD11b+ brain dendritic cell populations within the olfactory bulb [J].
D'Agostino, Paul M. ;
Kwak, Changsoo ;
Vecchiarelli, Haley A. ;
Toth, Judit Gal ;
Miller, James M. ;
Masheeb, Zahrah ;
McEwen, Bruce S. ;
Bulloch, Karen .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (16) :6175-6180
[4]   CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell-associated antigen [J].
Desch, A. Nicole ;
Randolph, Gwendalyn J. ;
Murphy, Kenneth ;
Gautier, Emmanuel L. ;
Kedl, Ross M. ;
Lahoud, Mireille H. ;
Caminschi, Irina ;
Shortman, Ken ;
Henson, Peter M. ;
Jakubzick, Claudia V. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2011, 208 (09) :1789-1797
[5]   Differential antigen processing by dendritic cell subsets in vivo [J].
Dudziak, Diana ;
Kamphorst, Alice O. ;
Heidkamp, Gordon F. ;
Buchholz, Veit R. ;
Trumpfheller, Christine ;
Yamazaki, Sayuri ;
Cheong, Cheolho ;
Liu, Kang ;
Lee, Han-Woong ;
Park, Chae Gyu ;
Steinman, Ralph M. ;
Nussenzweig, Michel C. .
SCIENCE, 2007, 315 (5808) :107-111
[6]   Peripheral CD103+ dendritic cells form a unified subset developmentally related to CD8α+ conventional dendritic cells [J].
Edelson, Brian T. ;
Wumesh, K. C. ;
Juang, Richard ;
Kohyama, Masako ;
Benoit, Loralyn A. ;
Klekotka, Paul A. ;
Moon, Clara ;
Albring, Joern C. ;
Ise, Wataru ;
Michael, Drew G. ;
Bhattacharya, Deepta ;
Stappenbeck, Thaddeus S. ;
Holtzman, Michael J. ;
Sung, Sun-Sang J. ;
Murphy, Theresa L. ;
Hildner, Kai ;
Murphy, Kenneth M. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (04) :823-836
[7]   The origin and development of nonlymphoid tissue CD103+ DCs [J].
Ginhoux, Florent ;
Liu, Kang ;
Helft, Julie ;
Bogunovic, Milena ;
Greter, Melanie ;
Hashimoto, Daigo ;
Price, Jeremy ;
Yin, Na ;
Bromberg, Jonathan ;
Lira, Sergio A. ;
Stanley, E. Richard ;
Nussenzweig, Michel ;
Merad, Miriam .
JOURNAL OF EXPERIMENTAL MEDICINE, 2009, 206 (13) :3115-3130
[8]   Dendritic Cell and Macrophage Heterogeneity In Vivo [J].
Hashimoto, Daigo ;
Miller, Jennifer ;
Merad, Miriam .
IMMUNITY, 2011, 35 (03) :323-335
[9]   Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation [J].
Hattori, Takaaki ;
Saban, Daniel R. ;
Emami-naeini, Parisa ;
Chauhan, Sunil K. ;
Funaki, Toshinari ;
Ueno, Hiroki ;
Dana, Reza .
JOURNAL OF LEUKOCYTE BIOLOGY, 2012, 91 (04) :621-627
[10]   Characterization of Langerin-Expressing Dendritic Cell Subsets in the Normal Cornea [J].
Hattori, Takaaki ;
Chauhan, Sunil K. ;
Lee, Hyunsoo ;
Ueno, Hiroki ;
Dana, Reza ;
Kaplan, Daniel H. ;
Saban, Daniel R. .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2011, 52 (07) :4598-4604