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However, recent studies employing modern transcriptomics coupled with novel imaging modalities have discovered that neutrophils exhibit significant heterogeneity within organs and have complex functional roles ranging from tissue homeostasis to cancer and chronic pathologies. This has revised the view that neutrophils are simplistic butchers, and there has been a resurgent interest in neutrophils. The spleen was described as a granulopoietic organ more than 4 decades ago, and studies indicate that neutrophils are briefly retained in the spleen before returning to circulation after proliferation. Transcriptomic studies have discovered that splenic neutrophils are heterogeneous and distinct compared with those in blood. This suggests that a unique hematopoietic niche exists in the splenic microenvironment, i.e., capable of programming neutrophils in the spleen. During severe systemic inflammation with an increased need of neutrophils, the spleen can adapt by producing neutrophils through emergency granulopoiesis. In this review, we describe the structure and microanatomy of the spleen and examine how cells within the splenic microenvironment help to regulate splenic granulopoiesis. A focus is placed on exploring the increase in splenic granulopoiesis to meet host needs during infection and inflammation. Emerging technologies such as single-cell RNA sequencing, which provide valuable insight into splenic neutrophil development and heterogeneity, are also discussed. Finally, we examine how tumors subvert this natural pathway in the spleen to generate granulocytic suppressor cells to promote tumor growth.<\/jats:p>","DOI":"10.1093\/jleuko\/qiae220","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T23:27:37Z","timestamp":1730935657000},"source":"Crossref","is-referenced-by-count":20,"title":["New insights on extramedullary granulopoiesis and neutrophil heterogeneity in the spleen and its importance in disease"],"prefix":"10.1093","volume":"117","author":[{"given":"Rongxia","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University , 169 Donghu Road, Wuchang District, Wuhan, Hubei 430071 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women's Hospital, Harvard Medical School , 77 Ave Louis Pasteur, Boston, MA 02115 ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College , 288 Nanjing Road, Heping District, Tianjin 300020 ,","place":["China"]},{"name":"Tianjin Institutes of Health Science, Chinese Academy of Medical Sciences , 288 Nanjing Road, Heping District, Tianjin 300020 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6065-0684","authenticated-orcid":false,"given":"Pei Xiong","family":"Liew","sequence":"additional","affiliation":[{"name":"Immunology Center of Georgia, Augusta University , 1410 Laney Walker Blvd, Augusta, GA 30912 ,","place":["United States"]},{"name":"Department of Cellular Biology and Anatomy, Augusta University, 1434 Laney Walker Blvd, Augusta , GA 30912 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