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The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex

The intestinal mucosa represents one of the largest barrier sites of our body, having to withstand a constant exposure to a plethora of environmental insults (including dietary compounds, xenobiotics, metabolites and microorganisms). While our body has evolved tolerance/ignorance towards some of these factors deemed beneficial for the host, it requires constant maintenance of epithelial barrier integrity and ability to mount pro-inflammatory responses to protect against potentially harmful environmental insults. The intestinal epithelium and innate lymphoid cells (ILCs) are two fundamental players in safeguarding intestinal homeostasis. The goal of this thesis was to study how ILC development/functions and the regenerative capacity of the intestinal epithelium are shaped by the intestinal inflammatory and metabolic milieu. In study I, we investigated whether the pool of adult ILC progenitors in the bone marrow was able to sense and respond to peripheral inflammation. We found that increase in systemic levels of the cytokine Flt3L resulted in expansion of ILC precursors committed to helper ILCs. Although ILCs expand in inflammatory bowel disease patients, this axis does not take place in response to intestinal inflammation. However, in the context of malaria, increased levels of systemic Flt3L correlated with expansion of bone marrow ILC precursors, thus suggesting a potential role for inflammatory ILC lymphopoiesis during malaria. In study II, we explored how alteration in cholesterol metabolism affected the function of intestinal ILCs. We showed that ILC3s, through the receptor EBI2, sensed cholesterol metabolites (oxysterols) produced by colonic stromal cells. Activation of this pathway led to ILC3 migration and thus formation of colonic lymphoid tissues (cryptopatches and isolated lymphoid follicles). Migration of ILC3s to cryptopatches resulted in their acquired ability to produce interleukin (IL)-22, a key intestinal homeostatic cytokine. However, in the contex