Hematopoietic stem cells engineered to release cytokines: A way of targeting lymphoid organs to modulate immune response?

We investigated whether the stem cell that reconstitutes total erythropoiesis of a WBB6F1-W/Wv mouse differentiates into lymphoid lineage. The electrophoretic pattern of hemoglobin was used as a marker of the reconstitution; 3-phosphoglycerate kinase (PGK), an X chromosome- linked enzyme was used as a tool for estimating clonality. We injected 10(5) bone marrow cells of 5-FU treated C57BL/6-Pgk-1b/Pgk-1a female mice, in which each stem cell had either A-type PGK or B-type PGK due to random inactivation of one of two X chromosomes, into genetically anemic (WB x C57BL/6)F1-W/Wv (hereafter WBB6F1-W/Wv) mice that contained only B-type PGK. The recipient WBB6F1-W/Wv mice, in which erythropoiesis was reconstituted with donor cells for a long term, were killed and the PGK patterns of bone marrows, thymus, lymph nodes, and Peyer's patches were examined. A considerable amount of A-type PGK was detected in the lymphoid organs of the WBB6F1-W/Wv mice in which erythrocytes showed only A-type PGK when killed. In contrast, A-type PGK was scarcely detectable in the lymphoid organs of the WBB6F1-W/Wv mice in which erythrocytes showed only B-type PGK when killed. The present results suggest that the hematopoietic stem cells estimated by the erythropoiesis reconstituting assay differentiate into lymphoid lineage and that the long-term erythropoiesis reconstitution assay is useful for detecting the true primitive hematopoietic stem cells.

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Lymphoid differentiation of the hematopoietic stem cell that reconstitutes total erythropoiesis of a genetically anemic W/Wv mouse

Blood ◽

10.1182/blood.v73.5.1175.1175 ◽

1989 ◽

Vol 73 (5) ◽

pp. 1175-1179 ◽

Cited By ~ 11

Author(s):

T Nakano ◽

N Waki ◽

H Asai ◽

Y Kitamura

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Hematopoietic Stem Cells ◽

Bone Marrow Cells ◽

Electrophoretic Pattern ◽

Phosphoglycerate Kinase ◽

Lymphoid Organs ◽

Hematopoietic Stem ◽

Lymphoid Lineage

Abstract We investigated whether the stem cell that reconstitutes total erythropoiesis of a WBB6F1-W/Wv mouse differentiates into lymphoid lineage. The electrophoretic pattern of hemoglobin was used as a marker of the reconstitution; 3-phosphoglycerate kinase (PGK), an X chromosome- linked enzyme was used as a tool for estimating clonality. We injected 10(5) bone marrow cells of 5-FU treated C57BL/6-Pgk-1b/Pgk-1a female mice, in which each stem cell had either A-type PGK or B-type PGK due to random inactivation of one of two X chromosomes, into genetically anemic (WB x C57BL/6)F1-W/Wv (hereafter WBB6F1-W/Wv) mice that contained only B-type PGK. The recipient WBB6F1-W/Wv mice, in which erythropoiesis was reconstituted with donor cells for a long term, were killed and the PGK patterns of bone marrows, thymus, lymph nodes, and Peyer's patches were examined. A considerable amount of A-type PGK was detected in the lymphoid organs of the WBB6F1-W/Wv mice in which erythrocytes showed only A-type PGK when killed. In contrast, A-type PGK was scarcely detectable in the lymphoid organs of the WBB6F1-W/Wv mice in which erythrocytes showed only B-type PGK when killed. The present results suggest that the hematopoietic stem cells estimated by the erythropoiesis reconstituting assay differentiate into lymphoid lineage and that the long-term erythropoiesis reconstitution assay is useful for detecting the true primitive hematopoietic stem cells.

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CD150-dependent hematopoietic stem cells sensing of Brucella instructs myeloid commitment

10.1101/2021.03.31.437872 ◽

2021 ◽

Author(s):

Hysenaj Lisiena ◽

De Laval Bérengère ◽

Arce-Gorvel Vilma ◽

Bosilkovski Mile ◽

Gonzalez Gabriela ◽

...

Keyword(s):

Stem Cells ◽

Immune Response ◽

Membrane Protein ◽

Hematopoietic Stem Cells ◽

Outer Membrane ◽

Outer Membrane Protein ◽

Pathogenic Bacteria ◽

Myeloid Lineage ◽

Hematopoietic Stem ◽

Bacterial Outer Membrane

ABSTRACTSo far, hematopoietic stem cells (HSC) are considered the source of mature immune cells, the latter being the only ones capable of mounting an immune response. Recent evidence shows HSC can also directly sense cytokines released upon infection/inflammation and pathogen-associated molecular pattern interaction, while keeping a long-term memory of previous encountered signals. Direct sensing of danger signals by HSC induces early myeloid commitment, increases myeloid effector cell numbers and contributes to an efficient immune response. Here, using specific genetic tools on both host and pathogen sides, we show that HSC can directly sense B. abortus pathogenic bacteria within the bone marrow via the interaction of the cell surface protein CD150 with the bacterial outer membrane protein Omp25, inducing efficient functional commitment of HSC to the myeloid lineage. This is the first demonstration of a direct recognition of a live pathogen by HSC via CD150, which attests of a very early contribution of HSC to immune response.SUMMARYThis work provides first evidence HSC directly sense Brucella abortus via the bacterial outer membrane protein Omp25 and the HSC surface receptor CD150, leading to functional commitment of HSC to myeloid lineage and very early initiation of immune response.

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