bims-emyelo 2026-10-25 papers

Issue of 2026–10–25
four papers selected by
Robbin Kramer, Radboudumc

Clin Sci (Lond). 2026 Oct 22. pii: CS20261960. [Epub ahead of print]

Impact of splenic red pulp macrophages on hematopoiesis and their therapeutic effects against sepsis.

Xi Peng, Weiyun Cao, Shijun Fan, Qian Chen, Lin Xia, Chunyan Li, Yonglin Lu, Yajuan Zhang.

Patients with sepsis frequently experience dysregulation of hematopoietic function in the bone marrow-spleen axis, resulting in hematologic abnormalities, including anemia and leukopenia. We hypothesized that red pulp macrophages (RPMs) in the spleen contribute to hematopoiesis through the bone marrow-spleen axis in septic patients. We established the sepsis model by cecal ligation and puncture (CLP) surgery, and performed bone marrow transplantation (BMT) and splenic RPMs transplantation (RPMT) after CLP. We evaluated splenic RPMs, hematopoietic stem and progenitor cells (HSPCs; LSK cells), and multipotent progenitor 3 cells (MPP3) proliferation and immunomodulatory properties. We performed splenic transcriptome sequencing (RNA-seq) to uncover the mechanisms by which RPMs exert therapeutic effects against sepsis. Sepsis-induced myelosuppression at 24h and MDSCs accumulation at 72h were detected. Both BMT and RPMT effectively restored splenic RPMs and suppressed MDSCs, with RPMT exerting a greater effect on LSK and MPP3 proliferation. RNA-seq confirmed that both BMT and RPMT attenuated sepsis-associated inflammation. Notably, RPMT exerted more targeted effects on hematopoietic cell lineage, cell cycle progression, and energy metabolism than BMT. This study demonstrates that splenic RPMs play a crucial regulatory role in hematopoiesis through the bone marrow-spleen axis during sepsis.

Keywords: Bone marrow-spleen axis; Hematopoiesis; Sepsis; Splenic red pulp macrophages

DOI: https://doi.org/10.1042/CS20261960

Dev Reprod. 2026 Sep;30(3): 145-153

Glyoxalase 1 (GLO1) Deficiency Is Associated with Myeloid Skewing and Altered Inflammatory Responses.

Ji-Hye Jung, Ji-Young Kim, Suji Jeong, Ji Yoon Lee, Seon-Sook Han, Seok-Ho Hong.

Glyoxalase 1 (GLO1) is involved in cellular adaptation to metabolic and oxidative stress, however, its role in regulating immune homeostasis remains poorly understood. Here, we used Glo1 knockout (Glo1-KO) mice to investigate the effects of GLO1 deficiency on bone marrow (BM) hematopoietic composition and the pulmonary inflammation environment. Flow cytometric analysis revealed alterations in BM myeloid-derived suppressor cell population, in Glo1-KO mice. In the lung GLO1 deficiency was accompanied by increased expression of inflammation and tissue-remodeling-associated genes, indicating an altered pulmonary inflammation milieu. Together, these findings demonstrate that GLO1 deficiency is associated with coordinated changes in hematopoietic immune environments and suggest that GLO1 may influence immune regulation across hematopoietic and peripheral tissue compartments.

Keywords: Glyoxalase 1; Hematopoiesis; Immune homeostasis; Pulmonary inflammation

DOI: https://doi.org/10.12717/DR.2026.30.3.145

JCI Insight. 2026 Oct 22. pii: e209595. [Epub ahead of print]11(20):

Patient-derived neomorphic SEPTIN6 mutations induce hematopoietic stem cell senescence underlying congenital neutropenia and myelodysplasia.

Safa F Mohamad, Meaghan McGuinness, Yu Zhou, Xin Jiang, Gabriele Casirati, Adele Mucci, Sara Canovas Nunes, Akiko Shimamura, Pietro Genovese, David A Williams.

Septins are RAS-like GTP-binding proteins involved in cytoskeletal organization and cellular division. We previously described 2 pediatric patients harboring SEPT6 germline mutations (GM1: SEPT6 c.1282T>C and GM2: SEPT6 c.1282T>A) presenting with congenital neutropenia associated with the development of myelodysplastic syndrome. In one patient, an additional somatic mutation (SM: SEPT6 c.43C>T) was detected at a low allelic fraction in the BM. Here, we describe the consequences of these mutations for hematopoiesis. Transgenic expression or gene editing of GM1 or GM2 in human CD34+ cells led to enlarged, multinucleated cells associated with accelerated exhaustion and premature senescence of hematopoietic stem and progenitor cells (HSPCs). Senescence defects were associated with the upregulation of mTOR phosphorylation, and pharmacologic inhibition of the mTOR pathway resulted in rescue of senescence. In parallel, HSPCs exhibited marked mitochondrial abnormalities, including increased expression of OPA-1, a key regulator of mitochondrial fusion, and enhanced oxygen consumption during mitochondrial respiration. Introduction of the SM in cis with GM1 mitigated all observed defects. Collectively, our findings demonstrate a gain-of-function mechanism underlying marrow failure in patients carrying germline SEPT6 mutations and suggest that acquisition of a secondary somatic SEPT6 variant may confer a compensatory effect within hematopoietic cells.

Keywords: Hematology; Hematopoietic stem cells; Oncology

DOI: https://doi.org/10.1172/jci.insight.209595

Front Immunol. 2026 ;17 1910059

Pre-transplant bone marrow lymphocyte subsets predict outcome after allogeneic stem cell transplantation.

Stefan Koeck, Gabriele Hetzenauer, Josia Fauser, Verena Petzer, Sieghart Sopper, Ines Peschel-Schaar, Dominik Wolf, David Nachbaur, Normann Steiner.

Introduction: Recent evidence has demonstrated that both donor- and recipient-derived immune cell subpopulations play a crucial role in various immune responses following allogeneic hematopoietic stem cell transplantation (HSCT). In this retrospective single center analysis, we investigated whether different lymphocyte subpopulations in the bone marrow (BM) of the recipient prior to HSCT might have an impact on outcome parameters after HSCT.
Methods: BM aspirates of 140 patients > 18 years of age receiving a HSCT between 2008 and 2022 were analyzed. BM aspiration was performed within 3 months prior to HSCT. Median time from aspiration to HSCT was 14 days (range 8-104 days). Lymphocyte subpopulations included CD19+ B cells, CD56+ NK cells, CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells, CD3+CD4-CD8- T cells and CD3+CD4+CD8+ T cells.
Results: High total lymphocytes > 37.35% (of leukocytes) correlated with an increased non-relapse mortality (NRM) at day 100 after HSCT, whereas high CD3+ T cells > 69.45% (of lymphocytes) and CD3+CD8+ T cells > 46.3% were associated with an increased risk for CMV infection. High NK cells > 8.8% resulted in an increased incidence for acute graft-versus host disease (GvHD). High CD19+ B cells > 13.1% resulted in a decreased incidence of chronic GvHD. In contrast, high CD4+ T cells > 49.3% were associated with an increased incidence of chronic GvHD.
Conclusion: Recipient-derived lymphocyte subpopulations within the BM prior to HSCT comprise the prognostic potential to assess post-HSCT related outcome parameters. In summary, a shift towards humoral immunity with a BM characterized by a B cell enriched and T cell/NK cell depleted microenvironment appears to be associated with a lower risk for post-HSCT complications.

Keywords: GvHD; allogenic stem cell transplantation; biomarker; flow cytometry; lymphocyte subpopulations; predictive

DOI: https://doi.org/10.3389/fimmu.2026.1910059