Reappraising the role of α5 integrin and the microenvironmental support in stress erythropoiesis.

We previously studied the role of β1 integrin and some of its different α partners relevant to erythropoiesis. Although clear and consistent answers regarding the role of α4β1 (VLA-4) were evident, the role of its companion integrin α5β1 (VLA-5) was clouded by inconsistent outcomes in all prior publications. Furthermore, the functional consequences of integrin deficiencies only in microenvironmental (ME) cells supporting erythroid cell expansion and maturation post stress have never been explored. In the study described here, we created several additional mouse models in the aim of addressing unanswered questions regarding functional consequences of single or combined integrin deficiencies in erythroid cells or only in ME supporting cells. Our novel and expansive data solidified the intrinsic requirement of both α4 and α5 integrins in erythroid cells for their proliferative expansion and maturation in response to stress; α5 integrin alone, deleted either early in all hematopoietic cells or only in erythroid cell, has only a redundant role in proliferative expansion and is dispensable for erythroid maturation. By contrast, α4 integrin, on its own, exerts a dominant effect on timely and optimal erythroid maturation. Deficiency of both α4 and α5 integrins in ME cells, including macrophages, does not negatively influence stress response by normal erythroid cells, in great contrast to the effect of ME cells deficient in all β1 integrins. Collectively the present data offer deeper insight into the coordination of different β1 integrin functional activities in erythroid cells or in ME cells for optimal erythroid stress response.

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