Lymphocyte traffic control by chemokines

Abstract

In contrast to the remarkable chemokine responses of phagocytes and monocytes that were documented early on, lymphocytes have been considered for a long time to be poor targets for chemokine action. This view has changed dramatically with the discovery that peripheral blood T cells need to be activated before they can migrate in response to inflammatory chemokines. These chemokines do not act on the bulk of resting T cells that are in circulation. The identification of a new group of chemokines that selects resting, as opposed to effector, T and B cells was very exciting. These inflammation-unrelated chemokines affect transendothelial migration and localization of progenitor and mature lymphocytes in lymphoid and nonlymphoid tissues. Here, we summarize the current view of chemokine-mediated lymphocyte traffic and focus on the molecular mechanisms by which T cell responses to chemokines are modulated. Recent developments in this area justify the hypothesis that the distinct migration patterns of lymphocytes throughout their life cycle--that is, during lymphopoiesis, antigen-dependent priming, inflammation and immune surveillance--are finely tuned by changing sets of chemokines that are selective for developmentally regulated chemokine receptors. Thus, the chemokine system assures that cell traffic during inflammatory responses occurs in the proper spatial and temporal fashion and disturbance of this system, therefore, can lead to inflammatory disease.

The chemokine system: tuning and shaping by regulation of receptor expression and coupling in polarized responses

“…One of the first observations made on this point was that monocytes exposed to bacterial lipopolysaccharide (LPS) showed a dramatic down-regulation of the receptor for CCL2/ MCP-1, CCR2 (29,30). This effect was associated with destabilization of the transcript, and was not dependent on induction of the agonist.…”

Up‐regulation of leukocyte CXCR4 expression by sulfatide: An L‐selectin‐dependent pathway on CD4+ T cells

“…Chemokines are a family of small (8-10 kDa) chemotactic cytokines that provide directional cues for leukocyte trafficking [3]. They are involved in HIV-1 infection, hematopoiesis, angiogenesis, embryonic de-velopment, tumor metastasis and graft rejection [3][4][5][6].…”

“…They are involved in HIV-1 infection, hematopoiesis, angiogenesis, embryonic de-velopment, tumor metastasis and graft rejection [3][4][5][6]. Stromal-derived factor 1, renamed CXCL12, is a potent chemoattractant for a variety of cells including lymphocytes, monocytes, dendritic cells, and hematopoietic stem cells [3].…”

“…They are involved in HIV-1 infection, hematopoiesis, angiogenesis, embryonic de-velopment, tumor metastasis and graft rejection [3][4][5][6]. Stromal-derived factor 1, renamed CXCL12, is a potent chemoattractant for a variety of cells including lymphocytes, monocytes, dendritic cells, and hematopoietic stem cells [3]. CXCL12 and its receptor CXCR4 play significant roles in immune and inflammatory responses, in lymphopoiesis, and in embryonic development; deletion of either CXCL12 or CXCR4 in rodent models is lethal [5,7].…”

CCR6 has a non‐redundant role in the development of inflammatory bowel disease

“…Chemokine control of leukocyte movement is not only important for immune system homeostasis and lymphoid organ architecture [5,6], but has also a direct effect on inflammatory cell recruitment to inflammation sites [7,8]. Chemokine overexpression has been observed in patients with ulcerative colitis or Crohn's disease [9][10][11][12][13].…”