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Skin Wounding-Induced Monocyte Expansion in Mice Is Not Abrogated by IL-1 Receptor 1 Deficiency.

ABSTRACT: The aim of this study was to determine whether skin wounding induces monocyte (Mo) expansion in bone marrow and whether IL-1R1 signaling regulates this process. Our data show that skin wounding increases myeloid lineage-committed multipotent progenitors (MPP3 subset) and Mo in bone marrow, but this expansion is not impaired in Il1r1-/- mice. We also demonstrate that M-CSF-induced differentiation of myeloid progenitors into Mo is not impaired by the loss of IL-1R1 ex vivo, indicating that IL-R1 deficiency does not abrogate myeloid progenitor differentiation potential. In addition, we observed modestly delayed wound closure in Il1r1-/- mice associated with higher frequency of Ly6Clo Mo in the circulation at baseline and in wounds early after injury. Thus, in contrast to other models of inflammation that involve IL-1R1-dependent monopoiesis, our results demonstrate that skin wounding induces Mo progenitor and Mo expansion independently of IL-1R1 signaling.

SUBMITTER: Barman PK

PROVIDER: S-EPMC6478552 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Skin Wounding-Induced Monocyte Expansion in Mice Is Not Abrogated by IL-1 Receptor 1 Deficiency.

Barman Pijus K PK Pang Jingbo J Urao Norifumi N Koh Timothy J TJ

Journal of immunology (Baltimore, Md. : 1950) 20190325 9

The aim of this study was to determine whether skin wounding induces monocyte (Mo) expansion in bone marrow and whether IL-1R1 signaling regulates this process. Our data show that skin wounding increases myeloid lineage-committed multipotent progenitors (MPP3 subset) and Mo in bone marrow, but this expansion is not impaired in Il1r1<sup>-/-</sup> mice. We also demonstrate that M-CSF-induced differentiation of myeloid progenitors into Mo is not impaired by the loss of IL-1R1 ex vivo, indicating t ...[more]

PMID: 30910860

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Project description:Melanocortin receptor 1 (MC1-R) is expressed in leukocytes, where it mediates anti-inflammatory actions. We have previously observed that global deficiency of MC1-R signaling perturbs cholesterol homeostasis, increases arterial leukocyte accumulation and accelerates atherosclerosis in apolipoprotein E knockout (Apoe-/-) mice. Since various cell types besides leukocytes express MC1-R, we aimed at investigating the specific contribution of leukocyte MC1-R to the development of atherosclerosis. For this purpose, male Apoe-/- mice were irradiated, received bone marrow from either female Apoe-/- mice or MC1-R deficient Apoe-/- mice (Apoe-/- Mc1re/e) and were analyzed for tissue leukocyte profiles and atherosclerotic plaque phenotype. Hematopoietic MC1-R deficiency significantly elevated total leukocyte counts in the blood, bone marrow and spleen, an effect that was amplified by feeding mice a cholesterol-rich diet. The increased leukocyte counts were largely attributable to expanded lymphocyte populations, particularly CD4+ T cells. Furthermore, the number of monocytes was elevated in Apoe-/- Mc1re/e chimeric mice and it paralleled an increase in hematopoietic stem cell count in the bone marrow. Despite robust leukocytosis, atherosclerotic plaque size and composition as well as arterial leukocyte counts were unaffected by MC1-R deficiency. To address this discrepancy, we performed an in vivo homing assay and found that MC1-R deficient CD4+ T cells and monocytes were preferentially entering the spleen rather than homing in peri-aortic lymph nodes. This was mechanistically associated with compromised chemokine receptor 5 (CCR5)-dependent migration of CD4+ T cells and a defect in the recycling capacity of CCR5. Finally, our data demonstrate for the first time that CD4+ T cells also express MC1-R. In conclusion, MC1-R regulates hematopoietic stem cell proliferation and tissue leukocyte counts but its deficiency in leukocytes impairs cell migration via a CCR5-dependent mechanism.

Dataset Information

Skin Wounding-Induced Monocyte Expansion in Mice Is Not Abrogated by IL-1 Receptor 1 Deficiency.

Publications

Skin Wounding-Induced Monocyte Expansion in Mice Is Not Abrogated by IL-1 Receptor 1 Deficiency.

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