IL-21 and IL-23 also contribute to the development of IL-21+CD4+ T cells, but at a much lesser extent. 1 response which keeps the disease in check, while the lepromatous form induces an often fatal Type 2 response3. DCs are endowed with enormous functional plasticity, which permits them to induce different immune responses according to the microenvironment. In addition, The BMX-IN-1 DC system is composed of subsets associated with the induction of different types of immunity. We have recently exhibited that two myeloid DC subsets in human skin, i.e., Langerhans cells (LCs) and CD14+ dermal DCs, are engaged in the induction of different types of adaptive immunity4. While LCs are very efficient at inducing CTL responses, CD14+ dermal DCs display a unique house to promote the development of antibody responses (Fig. 1). In this review, we will briefly summarize the phenotypical and functional differences between human LCs and CD14+ dermal DCs, and discuss how human DCs are involved in the regulation of humoral responses. Open in a separate windows Physique 1 CD14+ dermal DCs Rabbit Polyclonal to IRAK2 preferentially induce humoral immunity, while Langerhans cells induce cellular immunityUpon activation, epidermal LCs and CD14+ dermal DCs migrate to the secondary lymphoid organs through afferent lymphatics. Dermal DCs migrate into the outer paracortex, just beneath the B cell follicles, whereas LCs migrate into the T cell rich area. LCs are efficient at inducing high avidity-cytotoxic CD8+ T cell and Th1, BMX-IN-1 Th2, and Th22 responses. In contrast, CD14+ dermal DCs are efficient at inducing the differentiation of na?ve B cells into antibody-secreting cells (ASC) and at promoting the development of T follicular helper (Tfh) cells. CD4+ T cells primed by LCs might be efficient at helping the development of CTL responses. Epidermal LCs and CD14+ dermal DCs Human skin hosts at least three different mDC subsets. CD1ahighCD14?HLA-DR+ Langerhans cells (LCs) reside in epidermis, while CD1adimCD14?HLA-DR+ DCs (CD1a+ dermal DCs) and CD1a?CD14+HLA-DR+ DCs (CD14+ dermal DCs) are present in dermis 4. CD14+ dermal DCs express CD163 and FXIIIa, which are also expressed by dermal macrophages. However, CD14+ dermal DCs express CD11c, while dermal macrophages do not5. CD14+ dermal DCs express a broad spectrum BMX-IN-1 of surface C-type lectins including DC-SIGN, DEC-205, LOX-1, CLEC-6, Dectin-1, and DCIR6. In contrast, LCs express a more limited set, including Langerin and DCIR. Neither of the two dermal DC subsets express Langerin, an observation that contrasts with the presence of Langerin+ dermal DCs in mice7-9. CD14+ dermal DCs also express multiple TLRs realizing bacterial components, such as toll like receptor (TLR)1, 2, 4, 5, 6, 8, and 106, 10, suggesting their involvement in the induction of anti-bacterial immunity. LCs have been reported to express TLR1, 2, 3, 6, (7) and 1010-12, and to respond to ligands of TLR2 (peptideglycan11 and Pam3CysSerLys4 (Pam3CSK4)13) or TLR3 (Poly I:C11, 12). In contrast, a study showed that LCs poorly respond to TLR-ligands derived from bacteria, including TLR2, TLR4, and TLR510. Our microarray studies using of highly purified LCs failed to show much TLR expression6, while CD14+ dermal DCs showed significant expression. LCs promote CTL responses Human LCs are amazing at inducing CTL responses in vitro. For example, upon loading with tumor-derived peptides, LCs effectively prime peptide-specific na?ve CD8+ T cells, and induce their differentiation into CTLs that express high levels of cytotoxic molecules and are accordingly efficient at killing tumor cells4. Notably, induction of CTL response by LCs does not appear to be dependent on IL-12 or IFN-, as neither CD40 nor TLR activation do not induce LCs to secrete these cytokines4, 11, 12, 14. Instead, CD40-activation induces LCs to secrete IL-154, 14, which we surmise responsible for their capacity to induce potent CTL responses. This hypothesis is usually partly supported by the observation that externally added IL-15 enhances the ability of CD14+ dermal DCs to develop CTLs with high levels of cytotoxic granules6. LCs also induce a potent proliferation of allogeneic na?ve CD4+ T cells. Na?ve CD4+.