Osteopontin Is Involved in the Initiation of Cutaneous Contact Hypersensitivity by Inducing Langerhans and Dendritic Cell Migration to Lymph Nodes

Abstract

Osteopontin (OPN) is a chemotactic protein that attracts immune cells, to inflammatory sites. The sensitization phase of allergic cutaneous contact hypersensitivity (CHS) requires the migration of Langerhans cells/dendritic cells (LCs/DCs) from skin to draining lymph nodes. Characterizing OPN function for LC/DC migration we found upregulated OPN expression in hapten sensitized skin and draining lymph nodes. OPN induces chemotactic LC/DC migration, initiates their emigration from the epidermis, and attracts LCs/DCs to draining lymph nodes by interacting with CD44 and αv integrin. Furthermore, OPN-deficient mice have a significantly reduced CHS response that correlates with an impaired ability of OPN-deficient mice to attract LCs/DCs to draining lymph nodes. In conclusion, OPN is an important factor in the initiation of CHS by guiding LCs/DCs from skin into lymphatic organs.

Osteopontin: Role in immune regulation and stress responses

“…4.3). It has been reported that OPN deficiency reduces the recruitment of macrophages, neutrophils and dendritic cells Koh et al, 2007;Weiss et al, 2001). These results imply that OPN allows the expression of chemokines that may crucially influence cell recruitment during an inflammatory challenge.…”

“…Neutrophils (the majority of PMNs) are the primary responder to exogenous and endogenous stimuli and rapidly infiltrate the injured tissue to initiate an innate host defense. OPN is a chemoattractant for neutrophils (Weiss et al, 2001;Banerjee et al, 2006;Koh et al, 2007). Activated neutrophils release proteases and cytotoxic mediators in combination with phagocytosis and respiratory bursts to eliminate invading infectious agents.…”

“…Blockade of OPN with anti-OPN antibody reduces co-stimulatory molecule and class II molecule expression on human monocyte-derived DCs and promotes apoptosis of mature DCs (Kawamura et al, 2005). OPN was implicated in DC migration in research demonstrating that OPN initiates Langerhans cells/dendritic cell emigration from the epidermis and attracts them to draining lymph nodes by interacting with CD44 and α v integrin (Weiss et al, 2001). OPN-deficient mice have shown a significantly reduced contact hypersensitivity reaction possibly due to an impaired ability to attract Langerhans cells/DCs to draining lymph nodes.…”

“…OPN is a chemoattractant for many immune cells, including neutrophils (Koh et al, 2007), dendritic cells (Weiss et al, 2001), macrophages and T cells . It has been demonstrated both in vitro and in vivo that OPN directly induces chemotaxis and also indirectly facilitates migration of these cells to other chemoattractants ).…”

CD44 in hematological neoplasias

“…Additionally CD44 ligation triggers neutrophil apoptosis in vitro [88]. Similarly Langerhans and dendritic cell migration is mediated at least in parts by CD44, since antibodies against CD44 block OPN-induced cell migration to lymphatic organs in mice [89]. Also the proliferation of mast cells is regulated by CD44 [90].…”