IntroductionDendritic cells (DCs) play critical roles in the initiation of immune responses and induction of tolerance. 1 Balanced signaling transmitted via different activating and inhibitory receptors in DCs can regulate the functional status of DCs, thus determining duration and magnitude of T-cell responses. 2,3 Among the immune receptor families known to be expressed by DCs, the immunoglobulin superfamily (IgSF) seems to be unique in terms of structural features and roles in the regulation of DC development and function. 4 IgSF receptors are mostly type I membrane proteins, characterized by 1 or more immunoglobulin-like domains in the extracellular regions, which are pivotal in cell-cell recognition and interaction. IgSF receptors are abundant in the immune system and are widely distributed in lymphoid and myeloid cells including T cells, B cells, monocytes, DCs, and natural killer (NK) cells. It is well recognized that a vast quantity of IgSF molecules are involved in shaping the synapse formed between T cells and antigenpresenting cells (APCs), regulating various processes ranging from antigen (Ag) recognition and cell-cell interaction to signal transduction. 5 Many immune molecules belonging to the IgSF have recently been isolated and defined as key players in the innate and adaptive immune response, some of which act as inhibitory receptors with profound influence on immune responses. Inhibitory receptors are characterized by the presence of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic regions. Upon engagement with ligands, ITIMs contained in the inhibitory receptors serve as scaffolds for recruitment of protein-tyrosine phosphatases to mediate negative signaling, 6 maintaining adequate thresholds for cell activation to avoid irrelevant cell activation and induction of autoimmunity. 7 Considering the critical roles of DCs in the immune response, much attention has been focused on the isolation and functional analysis of receptors on DCs, especially on inhibitory receptors. Immunoglobulin-like transcript 3 (ILT3) and ILT4, 2 Ig superfamily receptors containing ITIMs, can negatively regulate antigen presentation, T-cell costimulation, and cytokine production by DCs. Up-regulation of ILT3/ILT4 by suppressor T cells is responsible for the tolerogenecity of monocytes and DCs. 8,9 Similarly, paired immunoglobulin-like inhibitory receptor B (PIR-B), a murine homologue of ILT4, has also been defined as a key negative regulator of DC functions, and impaired maturation of DCs and imbalanced T helper 1 (Th1) and Th2 immune responses occurred in PIR-B Ϫ/Ϫ mice. 10,11 Despite the fact that many inhibitory receptors belonging to Ig superfamily have been identified, unidentified members expressed by DCs remain to be isolated and investigated, and the identification of novel inhibitory immunoreceptors should further elucidate the sophisticated interactions between DCs and T cells. 13 where CMRF35-A and at least 6 other genes constitute an Ig family. Members of this family are involved ...

(2014) Critical role of SCD1 in autophagy regulation via lipogenesis and lipid rafts-coupled AKT-FOXO1 signaling pathway, Autophagy, 10:2, 226-242,

We previously showed that naive CD4+ Th cells acquire peptide-MHC class I (pMHC I) and costimulatory molecules from OVA-pulsed dendritic cells (DCOVA), and act as Th-APCs in stimulation of CD8+CTL responses. In this study, we further demonstrated that naive CD8+ cytotoxic T (Tc) cells also acquire pMHC I and costimulatory CD54 and CD80 molecules by DCOVA stimulation, and act as Tc-APC. These Tc-APC can play both negative and positive modulations in antitumor immune responses by eliminating DCOVA and neighboring Tc-APC, and stimulating OVA-specific CD8+ central memory T responses and antitumor immunity. Interestingly, the stimulatory effect of Tc-APC is mediated via its IL-2 secretion and acquired CD80 costimulation, and is specifically targeted to OVA-specific CD8+ T cells in vivo via its acquired pMHC I complexes. These principles could be applied to not only antitumor immunity, but also other immune disorders (e.g., autoimmunity).

Co-administration of local irradiation and intratumoral DC injection may be a promising strategy for treating radiosensitive tumors and eliminating metastasis in the clinic.