The potential role of CD44+ monocytes in mediating hyperinflammatory response in bronchopulmonary dysplasia in very premature infants.

He, Yi; Zhou, Yingzhi; Liu, Qingqing; Wang, Nianrong · Pediatr Res · 2026

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Abstract

Although roles of CD44 in the genetic predisposition for bronchopulmonary dysplasia (BPD) has been recognized, the immune characteristics of CD44+ monocytes in BPD are unclear. We aimed to (1) compare the expression and function of CD44 on monocytes in BPD and non-BPD infants; (2) explore the roles of CD44 on monocytes in hyperoxia-induced inflammation. Flow cytometry assessments of the expression pattern and cytokine-secreting response upon LPS stimulation of CD44+ monocytes were conducted using peripheral blood samples from BPD infants (n = 80) and non-BPD infants (n = 106). The role of CD44 on monocytes was validated in hyperoxia exposure. CD44 expression and inflammatory cytokine secretion ability increased with postmenstrual age. The ability of CD44+ monocytes to secrete IL-6 and TNF-α was significantly greater than that of CD44-monocytes. Compared with those of non-BPD infants, the response capacity of the monocytes in BPD infants to secret IL-6 and TNF-α, especially TNF-α sourced from CD44+ intermediate monocytes, was greater upon LPS stimulation. CD44 expression significantly increased in hyperoxia, and CD44 knockdown significantly ameliorated the inflammation induced by hyperoxia. CD44+ monocytes played important roles in mediating the hyper-inflammatory response in BPD. One specific subpopulation, TNF-α+/CD44+intermediate monocytes, might be a valuable marker for identifying BPD. 1. This study revealed the key role of an immune cell subtype-CD44+ monocytes-in hyperoxia-induced bronchopulmonary dysplasia (BPD) and characterized the expression and function of CD44+ monocytes between premature infants with BPD and those without BPD. 2. CD44 was closely associated with the proinflammatory cytokine secretion capacity of monocytes. A specific subpopulation-TNF-α+/CD44+ intermediate monocytes- might serve as a valuable marker for the identification of BPD in the future. 3. Our findings added new evidence of the association between CD44+ monocytes and BPD pathogenesis, which provided new insights into the immune mechanisms for BPD.