Th2 lymphocytes migrating to the bone marrow under high-altitude hypoxia promote erythropoiesis via activin A and interleukin-9.
The mechanism of accelerated erythropoiesis under the hypoxic conditions of high altitude (HA) remains largely obscure. Here, we investigated the potential role of bone marrow (BM) T cells in the increased production of erythrocytes at HA. We found that mice exposed to a simulated altitude of 6,000 m for 1-3 weeks exhibited a significant expansion of BM CD4+ cells, mainly caused by increasing T helper 2 (Th2) cells. Using a coculture model of BM T cells and hematopoietic stem/progenitor cells, we observed that BM CD4+ cells from hypoxic mice induced erythroid output more easily, in agreement with the erythroid-enhancing effect observed for Th2-condition-cultured BM CD4+ cells. It was further demonstrated that elevated secretion of activin A and interleukin-9 by BM Th2 cells of hypoxic mice promoted erythroid differentiation of hematopoietic stem/progenitor cells and the growth of erythroblasts, respectively. Our study also provided evidence that the CXCL12-CXCR4 interaction played an important role in Th2 cell trafficking to the BM under HA conditions. These results collectively suggest that Th2 cells migrating to the BM during HA exposure have a regulatory role in erythropoiesis, which provides new insight into the mechanism of high altitude polycythemia.
Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
Peng
P
Li
Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
Shan-jun
SJ
Zheng
Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
Chun-hua
CH
Jiang
Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
Si-min
SM
Zhou
Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
Huai-jun
HJ
Tian
Department of High Altitude Military Hygiene, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China.
Gang
G
Zhang
Department of Pathophysiology and High Altitude Physiology, College of High Altitude Military Medicine, Third Military Medical University, Chongqing, China; Key Laboratory of High Altitude Medicine, Ministry of Education, Chongqing, China; The Key Laboratory of High Altitude Medicine, People's Liberation Army, Chongqing, China. Electronic address: gaoyuan2004@163.com.
Yu-qi
YQ
Gao
D028341:Activins / Q000378:metabolism*; D000531:Altitude; D000532:Altitude Sickness / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D004920:Erythropoiesis; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D016906:Interleukin-9 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011086:Polycythemia / Q000378:metabolism* / Q000473:pathology; D019718:Receptors, CXCR4 / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism* / Q000473:pathology
C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D016906:Interleukin-9; D019718:Receptors, CXCR4; C422405:activin A; D028341:Activins