PMID- 32916215 OWN - NLM STAT- MEDLINE DCOM- 20210114 LR - 20220413 IS - 1873-2399 (Electronic) IS - 0301-472X (Print) IS - 0301-472X (Linking) VI - 90 DP - 2020 Oct TI - Interleukin 7 receptor is required for myeloid cell homeostasis and reconstitution by hematopoietic stem cells. PG - 39-45.e3 LID - S0301-472X(20)30359-3 [pii] LID - 10.1016/j.exphem.2020.09.001 [doi] AB - Respiratory diseases are a leading cause of death worldwide, with vulnerability to disease varying greatly between individuals. The reasons underlying disease susceptibility are unknown, but there is often a variable immune response in lungs often. Recently, we identified a surprising novel role for the interleukin 7 receptor (IL7R), a primarily lymphoid-associated regulator, in fetal-specified, lung-resident macrophage development. Here, we report that traditional, hematopoietic stem cell-derived myeloid cells in the adult lung, peripheral blood, and bone marrow also depend on IL7R expression. Using single- and double-germline knockout models, we found that eosinophil numbers were reduced on deletion of IL7Ralpha. We then employed two Cre recombinase models in lineage tracing experiments to test whether these cells developed through an IL7Ralpha+ pathway. Despite the impact of IL7Ralpha deletion, IL7R-Cre labeled only a minimal fraction of eosinophils. We therefore examined the intrinsic versus extrinsic requirement for IL7R in the production of eosinophils using reciprocal hematopoietic stem cell transplantation assays. These assays revealed that extrinsic, but not eosinophil-intrinsic, IL7R is required for eosinophil reconstitution by HSCs in the adult lung. To determine which external factors may be influencing eosinophil development and survival, we performed a cytokine array analysis between wild-type and IL7Ralpha-deficient mice and found several differentially regulated proteins. These findings expand on our previous report that IL7R is required not only for proper lymphoid cell development and homeostasis, but also for myeloid cell homeostasis in tissues. CI - Copyright (c) 2020 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved. FAU - Cool, Taylor AU - Cool T AD - Institute for the Biology of Stem Cells, University of California-Santa Cruz, Santa Cruz, CA; Program in Biomedical Sciences and Engineering, Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA. FAU - Worthington, Atesh AU - Worthington A AD - Institute for the Biology of Stem Cells, University of California-Santa Cruz, Santa Cruz, CA; Program in Biomedical Sciences and Engineering, Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA. FAU - Poscablo, Donna AU - Poscablo D AD - Institute for the Biology of Stem Cells, University of California-Santa Cruz, Santa Cruz, CA; Program in Biomedical Sciences and Engineering, Department of Molecular, Cell, and Developmental Biology, University of California-Santa Cruz, Santa Cruz, CA. FAU - Hussaini, Adeel AU - Hussaini A AD - Institute for the Biology of Stem Cells, University of California-Santa Cruz, Santa Cruz, CA. FAU - Forsberg, E Camilla AU - Forsberg EC AD - Institute for the Biology of Stem Cells, University of California-Santa Cruz, Santa Cruz, CA; Biomolecular Engineering, University of California-Santa Cruz, Santa Cruz, CA. Electronic address: cforsber@ucsc.edu. LA - eng GR - F31 HL151199/HL/NHLBI NIH HHS/United States GR - R01 DK100917/DK/NIDDK NIH HHS/United States GR - R25 GM058903/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20200908 PL - Netherlands TA - Exp Hematol JT - Experimental hematology JID - 0402313 RN - 0 (Receptors, Interleukin-7) SB - IM MH - Animals MH - Female MH - Hematopoietic Stem Cells/*immunology MH - Homeostasis/genetics/*immunology MH - Lung/cytology/*immunology MH - Lymphocytes/cytology/immunology MH - Male MH - Mice MH - Mice, Knockout MH - Myeloid Cells/cytology/*immunology MH - Receptors, Interleukin-7/genetics/*immunology MH - Signal Transduction/genetics/*immunology PMC - PMC7951140 MID - NIHMS1630871 COIS- Competing interests: The authors have no conflicting financial interests. EDAT- 2020/09/12 06:00 MHDA- 2021/01/15 06:00 PMCR- 2021/10/01 CRDT- 2020/09/11 20:11 PHST- 2020/05/02 00:00 [received] PHST- 2020/09/01 00:00 [revised] PHST- 2020/09/02 00:00 [accepted] PHST- 2020/09/12 06:00 [pubmed] PHST- 2021/01/15 06:00 [medline] PHST- 2020/09/11 20:11 [entrez] PHST- 2021/10/01 00:00 [pmc-release] AID - S0301-472X(20)30359-3 [pii] AID - 10.1016/j.exphem.2020.09.001 [doi] PST - ppublish SO - Exp Hematol. 2020 Oct;90:39-45.e3. doi: 10.1016/j.exphem.2020.09.001. Epub 2020 Sep 8.