Differential expression of inflammatory chemokines by Th1‐ and Th2‐cell promoting dendritic cells: A role for different mature dendritic cell populations in attracting appropriate effector cells to peripheral sites of inflammation

Abstract

Summary Protective immunity to pathogens depends on efficient immune responses adapted to the type of pathogen and the infected tissue. Dendritic cells (DC) play a pivotal role in directing the effector T cell response to either a protective T helper type 1 (Th1) or type 2 (Th2) phenotype. Human monocyte-derived DC can be differentiated into Th1-, Th2-or Th1/Th2-promoting DC in vitro upon activation with microbial compounds or cytokines. Host defence is highly dependent on mobile leucocytes and cell trafficking is largely mediated by the interactions of chemokines with their specific receptors expressed on the surface of leucocytes. The production of chemokines by mature effector DC remains elusive. Here we assess the differential production of both inflammatory and homeostatic chemokines by monocyte-derived mature Th1/Th2-, Th1-or Th2-promoting DC and its regulation in response to CD40 ligation, thereby mimicking local engagement with activated T cells. We show that mature Th1-and Th1/Th2-, but not Th2-promoting DC, selectively express elevated levels of the inflammatory chemokines CCL2/MCP-1, CCL3/MIP-1 α , CCL4/MIP-1 β and CCL5/RANTES, as well as the homeostatic chemokine CCL19/ MIP-3 β . CCL21/6Ckine is preferentially expressed by Th2-promoting DC. Production of the Th1-attracting chemokines, CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC, is restricted to Th1-promoting DC. In contrast, expression of Th2-associated chemokines does not strictly correlate with the Th2-promoting DC phenotype, except for CCL22/MDC, which is preferentially expressed by Th2-promoting DC. Because inflammatory chemokines and Th1-associated chemokines are constitutively expressed by mature Th1-promoting DC and CCL22/MDC is constitutively expressed by mature Th2-promoting DC, we propose a novel role for mature DC present in inflamed peripheral tissues in orchestrating the immune response by recruiting appropriate leucocyte populations to the site of pathogen entry.

CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity

“…28 Furthermore, there are data demonstrating that CCL19 is expressed by DC in lymphoid tissues and that it strongly attracts naive T cells. 29,30,31 We therefore postulate that after intramuscular DNA injection, it is mainly CCL19 expression occurring in regional lymph nodes (in DC and other cells), which is responsible for increased recruitment of naive T cells and possibly DC. This results in enhanced expansion of antigen-specific T cells, which may migrate to the tumor site and mediate tumor rejection.…”

Major Secretory Antigens of the Helminth Fasciola hepatica Activate a Suppressive Dendritic Cell Phenotype That Attenuates Th17 Cells but Fails To Activate Th2 Immune Responses

“…rFhCL1 and rFhGST-si induce the secretion of chemokines from DCs. Recently, it was shown that Th1-promoting DCs selectively express elevated MIP-1␣ and promote recruitment of Th1 cells (20,32), while MIP-2, a chemokine associated with helminth infection (38), promotes the recruitment of Th2 cells. Given the role played by these chemokines in the selective homing of immune cells, we sought to characterize the profiles of MIP-1␣ (CCL3) and MIP-2 (CXCL2) chemokines produced by DCs following treatment with rFhCL1 and rFhGST-si.…”

CCL21 Expression Pattern of Human Secondary Lymphoid Organ Stroma Is Conserved in Inflammatory Lesions with Lymphoid Neogenesis

“…This pattern, which constituted the bulk of CCL21 expression in human LNs and in RA ELT, was less developed in tonsils where CCL21 ϩ SMA-negative cells were frequently observed, indicating that myofibroblast precursors or other cell types, such as DCs, may contribute to CCL21 production in specific conditions. 14,46,49 The existence of additional levels of regulation controlling SMA and CCL21 expression was also emphasized by the fact that both in normal as well as in inflamed tissues SMA ϩ cells can be recognized in the absence of CCL21.…”