Subject(s)
Chikungunya virus , Dendritic Cells/metabolism , Genetic Vectors , Lipopolysaccharide Receptors/genetics , Viral Envelope Proteins/metabolism , Animals , Antibodies, Viral/immunology , Antigen Presentation , Antigens/immunology , CD4-Positive T-Lymphocytes/cytology , Dendritic Cells/cytology , HeLa Cells , Humans , Inflammation , Insecta , Macrophages/metabolism , Recombinant Proteins/chemistry , T-Lymphocytes , Viral Envelope Proteins/chemistryABSTRACT
Inflammatory immune cells recruited at the site of chronic inflammation form structures that resemble secondary lymphoid organs (SLO). These are characterized by segregated areas of prevalent T- or B-cell aggregation, differentiation of high endothelial venules, and local activation of resident stromal cells, including lymphatic endothelial cells. B-cell proliferation and affinity maturation toward locally displayed autoantigens have been demonstrated at these sites, known as tertiary lymphoid structures (TLS). TLS formation during chronic inflammation has been associated with local disease persistence and progression, as well as increased systemic manifestations. While bearing a similar histological structure to SLO, the signals that regulate TLS and SLO formation can diverge and a series of pro-inflammatory cytokines have been ascribed as responsible for TLS formation at different anatomical sites. Moreover, for a long time the structural compartment that regulates TLS homeostasis, including survival and recirculation of leucocytes has been neglected. In this chapter, we summarize the novel data available on TLS formation, structural organization, and the functional and anatomical links connecting TLS and SLOs.
Subject(s)
Cellular Microenvironment , Neovascularization, Pathologic , Tertiary Lymphoid Structures/pathology , Animals , Biomarkers , Cell Survival/genetics , Cell Survival/immunology , Cytokines/metabolism , Humans , Immunity, Innate , Inflammation/etiology , Inflammation/metabolism , Inflammation/pathology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Multigene Family , Receptors, Tumor Necrosis Factor/metabolism , Signal Transduction , Tertiary Lymphoid Structures/genetics , Tertiary Lymphoid Structures/immunology , Tertiary Lymphoid Structures/metabolismABSTRACT
Epidermal Langerhans cells (LCs) and dermal dendritic cells (dDCs) capture cutaneous antigens and present them to T-cells in lymph nodes (LNs). The function of LCs and Langerin+ dDCs was extensively studied in the mouse, but their anatomical repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail-draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the cutaneous immune reaction.
