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Programming dendritic cells to induce TH2 and tolerogenic responses

Abstract

A fundamental puzzle in immunology is how the immune system decides what types of immune responses to launch against different stimuli. Although much is known about control of T helper type 1 (TH1) and TH17 responses, the mechanisms that initiate TH2 and T regulatory (Treg) responses remain obscure. Emerging studies suggest a fundamental role for the innate immune system, particularly dendritic cells (DCs), in this process. We review these studies, and suggest that the innate control of TH2 and Treg responses can be viewed as different hierarchies of organization, in which DCs, their innate receptors and signaling networks, and their interactions with other cells and local microenvironments represent different levels of the hierarchy.

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Figure 1: Dendritic cells and hierarchies of organization in the innate immune system.
Figure 2: Signaling pathways that inhibit IL-12 production and program DCs to induce TH2 responses.
Figure 3: Signaling pathways that program DCs to induce tolerogenic responses.

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Acknowledgements

We thank H. Nakaya for assistance with the figures. We gratefully acknowledge the generous support of the US National Institutes of Health and the Bill and Melinda Gates Foundation in our work. We regret not being able to cite many relevant references because of space limitations.

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Correspondence to Bali Pulendran.

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Pulendran, B., Tang, H. & Manicassamy, S. Programming dendritic cells to induce TH2 and tolerogenic responses. Nat Immunol 11, 647–655 (2010). https://doi.org/10.1038/ni.1894

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