TY  - JOUR
AU  - Borvak, Jozef 
AU  - Sahu, Mukesh 
AU  - Joy, Varun 
AU  - Singhal, Jyotsana 
AU  - Yadav, Sushma 
AU  - Oakford, Larry Xavier 
AU  - Bae, Sejong 
AU  - Lelsani, Poorna Chandra Rao 
AU  - Nangrani, Amit 
AU  - Singhal, Sharad Swaroop 
AU  - Awasthi, Yogesh Chandra 
AU  - Awasthi, Sanjay 
PY  - 2010
TI  - Ral-Binding Protein is Required for the Maturation and Function of Dendritic Cells
JF  - American Journal of Immunology
VL  - 6
IS  - 3
DO  - 10.3844/ajisp.2010.29.42
UR  - https://thescipub.com/abstract/ajisp.2010.29.42
AB  - Problem statement: Dendritic Cells (DCs) integrate responses of innate and adaptive immune system via transmitting pro-inflammatory and regulatory signals to naïve cells within draining lymph nodes. DCs have high capacity for endocytosis, both Clathrin-Dependent (CDE) and Caveolin-Dependent (CvDE). Approach: We have recently shown that ATP-hydrolysis by the multifunctional transporter protein RLIP76 is the primary determinant of the rate of CDE. Activation of CDE is necessary for DCs to internalize and process exogenous antigens. Thus, in present studies we investigated the role of RLIP76 in antigen uptake, maturation and T cell priming capacity of monocyte-derived DCs. Results: Using flow cytometry, we demonstrate variable surface expression of RLIP76 on immature DCs generated from peripheral blood mononuclear cells from healthy individuals. Studies on the effect of anti-RLIP76 antibodies on endocytosis of DC-specific C-type Lectin Receptors (CLRs) (DC-SIGN and DEC-205) and on co-localization of these receptors with MHC-class II were conducted using confocal microscopy. RLIP76-specific antibodies suppressed the maturation of DCs and the expression of typical activation markers and co-stimulatory and adhesion molecules including CD83, HLA-DR, HLA-ABC, CD40, CD80 and CD38. They also inhibited the stimulating potency of DCs in allogeneic Mixed Leukocyte Reaction (allo-MLR). Conclusions: We conclude that RLIP76 is necessary for activation, membrane trafficking and functional maturation of DCs. Further exploration of the role of RLIP76 in DC biology is warranted and may provide promising means in DC-based immunotherapies.