Regulation of humoral and cellular gut immunity by lamina propria dendritic cells expressing Toll-like receptor 5

Uematsu S. et al 2008. Nat Immunol. 9(7):769-76.

Speaker: Yi-Ping Lin (林宜平)                                    Time: 15:00-16:00, Dec 3, 2008

Commentator: Dr. Huan-Yao Lei (黎煥耀)               Place: Room 601

Abstract:

　　Mucosal-associated immune system (MALT), which include gut-associated lymphoid tissue (GALT)、nasal-associated lymphoid tissue (NALT) and bronchus- associated lymphoid tissue (BALT), protect our bodies away from invasion of pathogens. In the MALT, especially the GALT, a supporting connective tissue lied under the epithelium is called the lamina propria (LP) containing many functional lymphocytes. Recent researches have found that macrophages and dendritic cells (DCs) in the intestinal LP can maintain the tolerance in the presence of commensal flora and arise the destructive immune response to the pathogens which penetrated through the epithelium [1] [2]. But the exactly subsets and the role in immune response about the LP cells is not clear. Depending on the expression level of CD11b and CD11c, Uematsu’s group used flow cytometry to isolate four cell subsets from the intestinal LP. They identified one of the cell subset expressed CD11b^hiCD11c^hi, are a kind of DC. These CD11b^hiCD11c^hiLPDCs also express high level TLR-5, which can recognize bacterial flagellin. Then Uematsu’s group discovered that these LPDCs can produce retinoic acid (RA), which gives LPDCs the ability to induce GALT-independent IgA synthesis. Next, they checked the role of LPDCs in T-cell development. These LPDCs can lead T cell differentiation to T_h1 and T_h17 cells. Interestingly, RA, the product of LPDCs, can also regulate the IL-17-producing T helper cells in a dose-dependent pathway. In addition, they use Salmonella typhimurium to infect the mice. The mice which immunized S. typhimurium flagellin-loaded wild-type LPDCs can partially defense the lethal menace to the infection of S. typhimurium. In conclusion, Uematsu’s group characterized the LPDCs expressed highly TLR-5 can induce local IgA producing and systemic T cell response. This observation shows the important role about LPDSc in immune response, and provides a potential target to the development of mucosal vaccine as well as therapy for some autoimmune disease.

References:

1. Denning TL et al. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17–producing T cell responses. Nat Immunol. 2007. 8(10):1086-94.

2. Sansonetti PJ. War and peace at mucosal surfaces. Nat Rev Immunol. 2004. 4(12):953-64.