TY - JOUR T1 - Expression of interferon regulatory factor 8 in human lung dendritic cell subsets JF - European Respiratory Journal JO - Eur Respir J VL - 40 IS - Suppl 56 SP - P813 AU - Fien Verhamme AU - Ken Bracke AU - Geert Van Pottelberge AU - Guy Joos AU - Guy Brusselle Y1 - 2012/09/01 UR - http://erj.ersjournals.com/content/40/Suppl_56/P813.abstract N2 - Disease-causing mutations in the transcription factor interferon regulatory factor 8 (IRF8) gene impair differentiation of mononuclear phagocytes into dendritic cells (DC) and confer susceptibility to mycobacterial disease. In autosomal recessive IRF8 deficiency, density of CD1a+ DC in the skin is very low, whereas numbers of Langerhans cells are normal, implicating important heterogeneity in dermal DC (Hambleton et al., N Engl J Med 2011). Since infection with Mycobacterium tuberculosis occurs via inhalation, we investigated the expression of IRF2, IRF4 and IRF8 in the 3 major resident pulmonary DC populations: Langerhans-type myeloid DC (LDC), interstitial-type myeloid DC (intDC) and plasmacytoid DC (pDC).Lung tissue was obtained from 4 subjects who underwent pneumectomy. DC were isolated by FACS from mononuclear cell suspensions of lung digests to obtain highly purified (>95%) DC subsets. LDC, intDC and pDC were identified as respectively langerin+, DC-SIGN+ and BDCA2+ cells in the low autofluorescent, CD3- and CD19- fraction. RNA was extracted and expression of IRF2, IRF4, IRF8 and housekeeping genes GADPH, HPRT1 and PPIA was analyzed by RT-PCR.Expression of IRF8 was significantly higher in pDC compared with both LDC and intDC. LDC had the lowest IRF8 expression (Figure 1). Expression of IRF2 and IRF4 did not differ between the DC subsets.These results suggest distinct roles of IRF8 in the development of human lung DC subsets. ER -