scholarly journals Essential role of submandibular lymph node dendritic cells in protective sublingual immunotherapy against murine allergy

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Noriaki Miyanaga ◽  
Hideaki Takagi ◽  
Tomofumi Uto ◽  
Tomohiro Fukaya ◽  
Junta Nasu ◽  
...  

AbstractWhile sublingual immunotherapy (SLIT) is known as an allergen-specific treatment for type-1 allergies, how it controls allergic pathogenesis remains unclear. Here, we show the prerequisite role of conventional dendritic cells in submandibular lymph nodes (ManLNs) in the effectiveness of SLIT for the treatment of allergic disorders in mice. Deficiency of conventional dendritic cells or CD4+Foxp3+ regulatory T (Treg) cells abrogates the protective effect of SLIT against allergic disorders. Furthermore, sublingual antigenic application primarily induces antigen-specific CD4+Foxp3+ Treg cells in draining ManLNs, in which it is severely impaired in the absence of cDCs. In ManLNs, migratory CD11b+ cDCs are superior to other conventional dendritic cell subsets for the generation of antigen-specific CD4+Foxp3+ Treg cells, which is reflected by their dominancy in the tolerogenic features to favor this program. Thus, ManLNs are privileged sites in triggering mucosal tolerance mediating protect effect of SLIT on allergic disorders that requires a tolerogenesis of migratory CD11b+ conventional dendritic cells.

1999 ◽  
Vol 73 (6) ◽  
pp. 4575-4581 ◽  
Author(s):  
Masahiko Makino ◽  
Satoshi Shimokubo ◽  
Shin-Ichi Wakamatsu ◽  
Shuji Izumo ◽  
Masanori Baba

ABSTRACT The development of human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is closely associated with the activation of T cells which are HTLV-1 specific but may cross-react with neural antigens (Ags). Immature dendritic cells (DCs), differentiated from normal donor monocytes by using recombinant granulocyte-macrophage colony-stimulating factor and recombinant interleukin-4, were pulsed with HTLV-1 in vitro. The pulsed DCs contained HTLV-1 proviral DNA and expressed HTLV-1 Gag Ag on their surface 6 days after infection. The DCs matured by lipopolysaccharides stimulated autologous CD4+ T cells and CD8+ T cells in a viral dose-dependent manner. However, the proliferation level of CD4+ T cells was five- to sixfold higher than that of CD8+ T cells. In contrast to virus-infected DCs, DCs pulsed with heat-inactivated virions activated only CD4+ T cells. To clarify the role of DCs in HAM/TSP development, monocytes from patients were cultured for 4 days in the presence of the cytokines. The expression of CD86 Ag on DCs was higher and that of CD1a Ag was more down-regulated than in DCs generated from normal monocytes. DCs from two of five patients expressed HTLV-1 Gag Ag. Furthermore, both CD4+ and CD8+ T cells from the patients were greatly stimulated by contact with autologous DCs pulsed with inactivated viral Ag as well as HTLV-1-infected DCs. These results suggest that DCs are susceptible to HTLV-1 infection and that their cognate interaction with T cells may contribute to the development of HAM/TSP.


2001 ◽  
Vol 356 (1406) ◽  
pp. 177-184 ◽  
Author(s):  
Charles Weissmann ◽  
Alex J. Raeber ◽  
Fabio Montrasio ◽  
Ivan Hegyi ◽  
Rico Frigg ◽  
...  

Following intracerebral or peripheral inoculation of mice with scrapie prions, infectivity accumulates first in the spleen and only later in the brain. In the spleen of scrapie–infected mice, prions were found in association with T and B lymphocytes and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDCs) but not with non–B, non–T cells; strikingly, no infectivity was found in lymphocytes from blood of the same mice. Transgenic PrP knockout mice expressing PrP restricted to either B or T lymphocytes show no prion replication in the lymphoreticular system. Therefore, splenic lymphocytes either acquire prions from another source or replicate them in dependency on other PrP–expressing cells. The essential role of FDCs in prion replication in spleen was shown by treating mice with soluble lymphotoxin–β receptor, which led to disappearance of mature FDCs from the spleen and concomitantly abolished splenic prion accumulation and retarded neuroinvasion following intraperitoneal scrapie inoculation.


2008 ◽  
Vol 82 (12) ◽  
pp. 5962-5966 ◽  
Author(s):  
Ramon Wade ◽  
Nicole Brimer ◽  
Scott Vande Pol

ABSTRACT Papillomavirus E6 proteins are adapters that change the function of cellular regulatory proteins. The bovine papillomavirus type 1 E6 (BE6) binds to LXXLL peptide sequences termed LD motifs (consensus sequence LDXLLXXL) on the cellular protein paxillin that is a substrate of Src and focal adhesion kinases. Anchorage-independent transformation induced by BE6 required both paxillin and BE6-binding LD motifs on paxillin but was independent of the major tyrosine phosphorylation sites of paxillin. The essential role of paxillin in transformation by BE6 highlights the role of paxillin in the transduction of cellular signals that result in anchorage-independent cell proliferation.


2020 ◽  
Vol 205 (7) ◽  
pp. 1867-1877 ◽  
Author(s):  
Takaaki Oba ◽  
Toshifumi Hoki ◽  
Takayoshi Yamauchi ◽  
Tibor Keler ◽  
Henry C. Marsh ◽  
...  

2020 ◽  
Vol 78 ◽  
pp. 106031 ◽  
Author(s):  
Uttam Gupta ◽  
Sumit Kumar Hira ◽  
Ranjeet Singh ◽  
Ankush Paladhi ◽  
Prateek Srivastava ◽  
...  

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