Thymic Stromal Lymphopoietin-Mediated Extramedullary Hematopoiesis Promotes Allergic Inflammation

• Published in: Immunity (Cambridge, Mass.) Vol. 39; no. 6; pp. 1158 - 1170
• Main Authors: Siracusa, Mark C., Saenz, Steven A., Tait Wojno, Elia D., Kim, Brian S., Osborne, Lisa C., Ziegler, Carly G., Benitez, Alain J., Ruymann, Kathryn R., Farber, Donna L., Sleiman, Patrick M., Hakonarson, Hakon, Cianferoni, Antonella, Wang, Mei-Lun, Spergel, Jonathan M., Comeau, Michael R., Artis, David
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 12.12.2013; Elsevier Limited
• Subjects: Animals; Bacterial infections; Cytokines; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Disease Models, Animal; Flow Cytometry; Gene Expression Profiling; Genotype & phenotype; Hematopoiesis, Extramedullary - immunology; Humans; Hypersensitivity - immunology; Immune system; Infections; Inflammation; Mice; Mice, Inbred C57BL; Pediatrics; Polymorphism, Genetic; Precursor Cells, B-Lymphoid - cytology; Rodents; Spleen; Spleen - cytology; Spleen - immunology; Studies; Trichinellosis - immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2013.09.016

Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern-recognition receptor (PRR)-expressing HSCs, EMH, and immune responses to microbial stimuli. However, whether EMH operates in broader immune contexts remains unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiated into effector cells including macrophages, dendritic cells, and granulocytes and that these cells contributed to type 2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway might operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity. [Display omitted] •TSLP elicits extramedullary hematopoiesis (EMH)•TSLP-elicited EMH promotes allergic inflammation•Exaggerated TSLP-elicited EMH might contribute to human allergic disease•EMH is a conserved mechanism of innate immunity