02333nas a2200385   4500000000100000008004100001260001600042653001500058653002500073653002500098653002000123653001400143653002000157653005300177653001100230653002600241653001400267653002700281653001800308100001100326700001500337700001300352700001500365700001000380700001600390700001000406700001200416700001400428700001400442245009900456300001200555490000800567520135800575022001401933       2007                            d  c2007 Dec 1510aAntibodies10aAntigen Presentation10aCell Differentiation10aCells, Cultured10aCytokines10aDendritic Cells10aGranulocyte-Macrophage Colony-Stimulating Factor10aHumans10aLymphocyte Activation10aMonocytes10aReceptors, Immunologic10aT-Lymphocytes1 aLee DJ1 aSieling PA1 aOchoa MT1 aKrutzik SR1 aGuo B1 aHernandez M1 aRea T1 aCheng G1 aColonna M1 aModlin RL00aLILRA2 activation inhibits dendritic cell differentiation and antigen presentation to T cells.  a8128-360 v1793 a<p>The differentiation of monocytes into dendritic cells (DC) is a key mechanism by which the innate immune system instructs the adaptive T cell response. In this study, we investigated whether leukocyte Ig-like receptor A2 (LILRA2) regulates DC differentiation by using leprosy as a model. LILRA2 protein expression was increased in the lesions of the progressive, lepromatous form vs the self-limited, tuberculoid form of leprosy. Double immunolabeling revealed LILRA2 expression on CD14+, CD68+ monocytes/macrophages. Activation of LILRA2 on peripheral blood monocytes impaired GM-CSF induced differentiation into immature DC, as evidenced by reduced expression of DC markers (MHC class II, CD1b, CD40, and CD206), but not macrophage markers (CD209 and CD14). Furthermore, LILRA2 activation abrogated Ag presentation to both CD1b- and MHC class II-restricted, Mycobacterium leprae-reactive T cells derived from leprosy patients, while cytokine profiles of LILRA2-activated monocytes demonstrated an increase in TNF-alpha, IL-6, IL-8, IL-12, and IL-10, but little effect on TGF-beta. Therefore, LILRA2 activation, by altering GM-CSF-induced monocyte differentiation into immature DC, provides a mechanism for down-regulating the ability of the innate immune system to activate the adaptive T cell response while promoting an inflammatory response.</p>  a0022-1767