Since the discovery of dendritic cells (DCs) by the Nobel laureate Professor Ralph Steinman et al. in 1973, a plethora of literature has accumulated on the functional roles of DCs in humans and animal models. 1 DCs are involved in the innate sensing and modulation of adaptive immunity to pathogens. CD103+ DCs constitute a classical nonlymphoid DC subset that has an important role in generating immunity and maintaining tolerance. 2 Pulmonary CD103+ DCs (CD103+ PDCs), which reside in close association with the airway epithelium, are particularly critical in controlling T-cell immunity against lung infections. 2, 3 In this article, we discuss recent evidence that shines light on the role and mechanism of CD103+ PDCs in modulating CD8+ and CD4+ T-cell responses against various pathogens, including bacteria and viruses. A deeper understanding of CD103+ PDC function may provide new translational avenues for the development of vaccines and therapeutics against infectious diseases. Mouse CD103+ PDCs are phenotypically characterized by the expression of αE (CD103) β7, CD11chi, CD207, MHC-II, TLR3, XCR1, and Clec9a/DNGR1 but not CD64 and CD11b. 3 The transcription factors Batf3 and Irf8 are critical for the development of CD103+ PDCs, as shown by the lack of these DCs in Batf3-or Irf8-deficient mice. 3 Following pulmonary infection, CD103+ PDCs upregulate costimulatory molecules (CD40, CD80, and CD86), produce large quantities of several cytokines (IL-4, IL-13, IL-12, IL-10, IL-23, and IL-6), migrate to the lung-draining mediastinal lymph nodes, and prime naive CD4+ and CD8+ T cells to induce antigen-specific immune responses. 4-6 Recent studies indicate that CD103+ DCs, along with lymphoid CD8α+ DCs, form a new class of DCs referred to as type 1 DCs (DC1s), which express the chemokine receptor XCR1 and perform the unique function of cross-presenting exogenous antigens with MHC-I molecules to CD8+ T cells. 7 Owing to similar phenotypic and functional characteristics, human CD141/BDCA-3+ DCs are considered equivalent to murine DC1s. 8 Overall, these DCs constitute a unified DC subset in mice and humans that is developmentally and functionally related. An accumulating wealth of evidence stemming from mouse studies has focused on the function of CD103+ PDCs during viral and bacterial infections. 4, 6, 9 Upon challenge with respiratory influenza A virus or poxvirus infection, mice that lack CD103+ DCs, such as Batf3−/− and Clec9A− diphtheria toxin receptor transgenic mice, failed to induce protective immunity, in contrast to control mice, suggesting a protective role for CD103+ PDCs in viral infections. 6, 9, 10 Following influenza A virus infection, CD103+ PDCs acquired and processed apoptotic cell-associated viral antigens in their endocytic compartment, migrated to the mediastinal lymph nodes, and cross-presented the antigens on

MHC-I molecules to naive CD8+ T cells to elicit protective virusspecific cytotoxic responses. 6, 11 Interestingly, CD103+ PDCs could cross-present antigens from virally infected cells because of their ability to resist infection by influenza virus via a type I interferonmediated antiviral state. 6 On the other hand, ablation of CD103+ PDCs resulted in decreased production of IFN-γ by CD8+ T cells and reduced expression of the activation and transcription markers Ki67, CD25, and T-bet in these cells after respiratory vaccinia virus infection. 10 Liang Ng et al. 12 have further shown that CD103+ PDCs not only control cross-priming of CD8+ T cells but also regulate their migration, viability, and memory responses during influenza infection. In doing so, CD103+ PDCs induce …