Regulation of homeostatic chemokine expression and cell trafficking during immune responses.
The chemokines CCL21 and CXCL13 are immune factors that dictate homing and motility of lymphocytes and dendritic cells in lymphoid tissues. However, the means by which these chemokines are regulated and how they influence cell trafficking during immune responses remain unclear. We show that CCL21 and CXCL13 are transiently down-regulated within lymphoid tissues during immune responses by a mechanism controlled by the cytokine interferon-gamma. This modulation was found to alter the localization of lymphocytes and dendritic cells within responding lymphoid tissues. As a consequence, priming of T cell responses to a second distinct pathogen after chemokine modulation became impaired. We propose that this transient chemokine modulation may help orchestrate local cellularity, thus minimizing competition for space and resources in activated lymphoid tissues.
Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. mueller@microbio.emory.edu
Scott N
SN
Mueller
Karoline A
KA
Hosiawa-Meagher
Bogumila T
BT
Konieczny
Brandon M
BM
Sullivan
Martin F
MF
Bachmann
Richard M
RM
Locksley
Rafi
R
Ahmed
Mehrdad
M
Matloubian
D019264:Adoptive Transfer; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D019743:Chemokines, CXC / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D015536:Down-Regulation; D005260:Female; D006706:Homeostasis; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D016207:Cytokines; D012333:RNA, Messenger; D007371:Interferon-gamma