IgE-Mediated Mast Cell Activation Induces Langerhans Cell Migration In Vivo

Abstract

Langerhans cells and mast cells are both resident in large numbers in the skin and act as sentinel cells in host defense. The ability of mast cells to induce Langerhans cell migration from the skin to the draining lymph node in vivo was examined. Genetically mast cell-deficient (W/Wv) mice and control mice were sensitized with IgE Ab in the ear pinna. Seven to 14 days later, mice were challenged with Ag i.v. After a further 18–24 h, epidermal sheets and draining auricular lymph nodes were examined using Langerin/CD207 immunostaining. In mast cell-containing mice, a significant decrease in the number of Langerhans cells was observed at epidermal sites of mast cell activation. A significant increase in total cellularity and accumulation of Langerin-positive dendritic cells was observed in the auricular lymph nodes, draining the sites of IgE-mediated mast cell activation. These changes were not observed in W/Wv mice, but were restored by local mast cell reconstitution. Treatment of mast cell-containing mice with the H2 receptor antagonist cimetidine significantly inhibited the observed IgE/Ag-induced changes in Langerhans cell location. In contrast, Langerhans cell migration in response to LPS challenge was not mast cell dependent. These data directly demonstrate the ability of mast cells to induce dendritic cell migration to lymph nodes following IgE-mediated activation in vivo by a histamine-dependent mechanism.

Type 1 Diabetes in NOD Mice Unaffected by Mast Cell Deficiency

“…Secondly, our study, along with earlier studies (16), put into question the suggested ability of mast cells to control or modulate autoimmunity-promoting adaptive immune response (14,46). Mast cell deficiency did not affect the levels of conventional or regulatory T cells, B cells, or dendritic cells in the PLNs; moreover, T-cell activation, much of which had previously been suggested to be associated with mast cell function, was also unaffected by mast cell deficiency (23)(24)(25)(28)(29)(30)(31)(32)(33)(34)(35). Obviously, we refrain from extrapolating negative data obtained in experiments on arthritis, experimental autoimmune encephalomyelitis (16), and T1D (this study) to the potential roles of mast cells in other autoimmune responses or adaptive immunity in general.…”

“…Akin to humans, in the universally used nonobese diabetic (NOD) mouse model of T1D, the highest genetic contributor to disease susceptibility maps to the major histocompatibility complex (21,22). In view of the T-cell dependency of this disease and the putative roles of mast cells in the control of T-cell responses, which may occur via direct antigen presentation to either CD4 + or CD8 + T cells (23)(24)(25), by induction of T-cell migration to lymph nodes (26,27), by control of dendritic cell activation and migration to lymph nodes (28)(29)(30)(31), or by control of the Th1 versus Th2 skewing (32)(33)(34)(35), it has been postulated that mast cells are likely important players in the development of T1D (14,15,36).…”

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

“…In many of these studies, the end points assessed included the recruitment of particular immune cells, such as granulocytes 28,32,33,[57][58][59][60][61]63,64,[67][68][69][70] , DCs 62,64,65,71 or various subpopulations of lymphocytes 64,67,70,72 . Many of these studies also demonstrated that the lack of mast cells 54,[57][58][59][60][61][62][63][64]67,69,70 or a specific mast-cell product 28,32,33,54,60,63,67,68,70 also reduced the pathology associated with the immune response or impaired its effectiveness in promoting host resistance to infection.…”

Mast Cells Enhance T Cell Activation: Importance of Mast Cell Costimulatory Molecules and Secreted TNF

“…Moreover, studies using genetically mast cell-deficient mice have shown that mast cells can promote the migration of Langerhans cells from the epidermis upon hapten sensitization in a model of oxazolone-induced contact hypersensitivity (6) and that the IgEand Ag-dependent activation of skin mast cells can promote the migration of skin DCs to local draining lymph nodes by a mechanism that is in part H 2 histamine receptor-dependent (7).…”