Transcription profiling of mouse natural helper cell

ABSTRACT: Innate immune responses are important in combating various microbes during the early phases of infection. Natural killer (NK) cells are innate lymphocytes that, unlike T and B lymphocytes, do not express antigen receptors but rapidly exhibit cytotoxic activities against virus infected cells and produce various cytokines1,2. We report here a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity. These cells do not express lineage (Lin) markers but express c-Kit, Sca-1, IL-7R and IL-33R. Similar lymphoid clusters were found in both human and mouse mesentery and we term this tissue â??FALCâ?? for fat-associated lymphoid cluster. FALC Lin-c-Kit+Sca-1+ cells are distinct from lymphoid progenitors3 and lymphoid tissue inducer (LTi) cells4. These cells proliferate in response to IL-2 and produce large amounts of Th2 cytokines such as IL-5, IL-6 and IL-13. IL-5 and IL-6 regulate B cell antibody production and self-renewal of B1 cells5-7. Indeed, FALC Lin-c-Kit+Sca-1+ cells support the self-renewal of B1 cells and enhance IgA production. IL-5 and IL-13 mediate allergic inflammation and protection against helminth infection8,9. Upon helminth infection and in response to IL-33, FALC Lin-c-Kit+Sca-1+ cells produce large amounts of IL-13, which leads to goblet cell hyperplasia, a critical step for helminth expulsion. In mice devoid of FALC Lin-c-Kit+Sca-1+ cells such goblet cell hyperplasia was not induced. Thus, FALC Lin-c-Kit+Sca-1+ cells are Th2-type innate lymphocytes and we propose that these cells be called â??natural helper cellsâ??. Experiment Overall Design: Natural helper cells (Lin- c-kit+ Sca-1+) were isolated from mesentery of C57BL/6 for RNA extraction and hybridization on Affymetrix microarrays. For the control of this experiment, we use double negative cells (DN2) from thymus of C57BL/6 or lymphoid tissue inducer cells (LTi). Thymic DN2 cells were prepared from adult thymocytes. Thymocytes were stained with magnetic beads conjugated with anti-CD4 and anti-CD8α mAbs and CD4-CD8- double negative (DN) cells were negatively sorted by AutoMACS. DN cells were further stained with anti-CD25 and anti-CD44 mAbs and CD25+CD44+ cells were sorted as DN2 cells on a FACSAria.Thy-1+CD4- LTi cells were prepared from fetal liver cells as described previously. c-Kit+α4β7+IL-7Rα+ fetal liver cells from day 13 embryos were cultured on TSt4 cells for 17 days.

ORGANISM(S): Mus musculus

SUBMITTER: kazuyo moro 

PROVIDER: E-GEOD-18752 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress