| Authors |
Klein BR, Smith JNP, Katabathula R, Rashmil R, Wilhelm SX, Chaudhary R, De
Carvalho KIL, Gao Z, Cordova BA, Irons EE, Kovacic B, Parsai S, Makarov V,
Petroze F, Tiwari R, Gerson SL, Xu R, Markowitz SD, Desai AB
|
| Submitted By |
Amar Desai on 9/9/2026 |
| Status |
Published |
| Journal |
Experimental hematology |
| Year |
2026 |
| Date Published |
9/3/2026 |
| Volume : Pages |
Not Specified : 105893 |
| PubMed Reference |
42692326 |
| Abstract |
Mast cells (MCs) are well known for their roles in immunity, but their influence
on hematopoietic stem cell (HSC) regulation remains poorly defined. Here, we
identify MC-derived histamine as a suppressor of hematopoiesis. MC-deficient
"SASH" mice exhibited increased bone marrow HSC frequency, a transcriptional
quiescence signature, and resistance to myeloablative chemotherapy, associated
with niche remodeling, including increased HSC-supportive stromal populations
and elevated maintenance factor expression, and improved engraftment of
wild-type donor cells. Reciprocal transplants showed this phenotype is driven by
the recipient niche rather than an HSC-intrinsic property, and MC-derived
secretory factors were directly sufficient to suppress HSCs in vitro and in
vivo. Pharmacologic H1 receptor blockade with cetirizine, an FDA-approved
inverse agonist, phenocopied the SASH model, expanding HSCs and enhancing both
early recovery and long-term reconstitution in transplant settings, while
exogenous histamine reversed the SASH phenotype. Supporting clinical relevance,
electronic health record analysis revealed that antihistamine use was associated
with elevated white blood cell counts in humans. These findings establish mast
cell-derived histamine as a suppressor of hematopoiesis and suggest that H1R
antagonism may offer a tractable strategy to enhance hematopoietic regeneration.
Teaser Abstract: Mast cell-derived histamine restrains hematopoietic stem cell
activity by shaping the bone marrow niche. Blocking histamine signaling with the
FDA-approved antihistamine cetirizine expands the stem and progenitor pool and
accelerates hematopoietic recovery after transplant, pointing to a repurposable
strategy for boosting blood regeneration in patients.
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