Reactive granulopoiesis depends on T-cell production of IL-17A and neutropenia-associated alteration of gut microbiota

Abstract

Granulopoiesis in the bone marrow adjusts cellular output as demand for neutrophils changes. Reactive granulopoiesis is induced by profound neutropenia, but its mechanism remains to be clarified. We herein explored its mechanisms using mouse models of syngeneic hematopoietic stem cell transplantation (SCT) and 5-fluorouracil-induced neutropenia. After SCT, T cell production of IL-17A was up-regulated. Neutrophil recovery was significantly delayed in IL-17A-deficient or T cell-deficient RAG1 −/− mice, and adoptive transfer of wild-type ( WT ) T cells facilitated neutrophil engraftment. Gut decontamination with oral antibiotics suppressed T cell production of IL-17A and impaired neutrophil recovery. Transplantation of fecal microbiota collected from neutropenic, not naive, mice promoted neutrophil recovery in these mice, suggesting that neutropenia-associated microbiota had a potential to stimulate reactive granulopoiesis. Our study uncovered a cross talk between gut microbiota and neutropenia after SCT and chemotherapy.

Diversity of the Japanese Gut Microbiome Analysis: Relative Approach Using Principal Component Analysis

“…However, PCA was able to reduce the dimensionality of compositional information. The analysis of beta and alpha diversity using multidimensional scaling was not good because it assumed no correlation between bacteria [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. ANOSIM, ADONIS, and other analyses may result in small p-values and small values of R and R-squared values.…”

“…Principal component analysis (PCA) and multidimensional scaling (MDS or principal coordinates analysis/PCoA) are often used for gut microbiome analyses [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. PCA and PCoA are types of unsupervised machine learning.…”

“…Gut microbiome analysis is a field of information engineering. Moreover, in recent years, bacteriological studies have sometimes been conducted using the results from the gut microbiome analysis [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, misinformation is pervasive in the human microbiome literature [6].…”

“…Many recent microbiome analyses have compared the proportions of compositional data. Many studies apply mathematical incorrect methods (multidimensional scaling, correlation coefficient and arithmetic means) for analyzing the gut microbiome [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Misinformation on microbiota analysis can cause great harm to bacteriology professionals.…”

“…However, most studies did not provide reasons for using the ratio of Bacteroidetes [11][12][13][14][15]. Moreover, many microbiota analyses have been performed assuming the same number of bacteria among individuals, with many standardized 10,000 OTU reads [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. However, the assumption that the number of bacteria is the same among individuals is a severe condition that is not necessarily met.…”