About this Research Topic
Given the success of Volume I of this Research Topic, we are pleased to announce the launch of “Innate Immune Cells and Inflammatory Mediators in Mucosal Pathologies: Volume II”.
Immune cells participate in maintaining homeostasis at mucosal tissues including lung and gut. The mucosal immune system is charged with the detection and elimination of pathogens while maintaining tolerance toward commensal bacteria and innocuous antigens. The disruption of this delicate balance leads to the development of pathologies affecting the gut, as in the case of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), celiac diseases or pathologies affecting the respiratory tract as asthma, cystic fibrosis or chronic obstructive pulmonary disease (COPD).
Notwithstanding the fact that epithelial cells play an essential role in the control of mucosal integrity and homeostasis, there is increasing evidence of the important contribution of innate immune cells in these phenomena. For instance, dendritic cells (DCs) play a central role as sentinels of damage or infection by patrolling the mucosal interface. In healthy mucosa, DCs have a tolerogenic phenotype which maintains the homeostasis by activating regulatory T cells. During pathological conditions, DCs perceive the signs of damage through pattern recognition receptors (PRR) and acquire an inflammatory phenotype that allows the activation of both innate and adaptive immune responses. DCs from IBD patients express increased levels of TLR2/TLR4 and co-stimulatory markers allowing them to promote T cell proliferation. Colonic CD103+ DCs, generally associated to tolerance, acquire the ability to release IL-6, IL-12 and TNF- in UC patients. In these conditions, CD103+ DCs do not generate Foxp3+ Treg but induce the differentiation of effector Th1 and Th17 cells. Likewise, in CD patients the production of pro-inflammatory cytokines by colonic DCs correlates with the periods of disease activity. Retinoid acid (RA) is required for optimal Treg induction by intestinal CD103+ DCs in the steady-state but these cells have a reduced expression of RA-generating enzymes in mice with UC. Surprisingly, it was shown that the effects of RA on the immune system depend on the context. In the presence of IL-15, RA induces the release of the pro-inflammatory cytokines IL-12 and IL-23 by DCs promoting intestinal inflammation.
In the lung, allergic asthma is associated with type 2 inflammatory responses. Chronic type 2 airway inflammation can become fibrotic increasing the risk of pulmonary infections or COPD. In addition to their potent immunogenic capacity, DCs can also play a central role in the evolution of tissue damage. DCs are not only activated by infection or injury but also by the complex milieu resulting for other innate cells signals and/or secretions. Neutrophils, eosinophils, basophils, mast cells, iNKT (invariant Natural Killer T cells), MAIT (Mucosal-Associated Invariant T cells), T and ILC (Innate Lymphoid Cells) have a central role in starting tissue damage through DCs activation. Throughout the inflammation, a complex cross-talk exists between these cells via their production of soluble mediators such as histamine, leukotrienes, prostaglandins, cytokines and alarmins.
A combination of approaches including in vitro, ex vivo and animal model-based studies have demonstrated the roles of DCs and the others innate or innate-like T cells cited above in several gut and lung pathologies.
In this Research Topic, we welcome the submission of Original Research, Review and Mini Review articles focusing on, but not limited to, the following subtopics:
1. How soluble mediators released by innate cells disrupt tolerance mechanisms
2. The role of innate cells and inflammatory mediators in gut and lung pathologies
3. Cross-talk between DCs and innate lymphocytes as a trigger of pathology
4. How innate inflammation affects epithelial barrier function inducing damage
Immune cells participate in maintaining homeostasis at mucosal tissues including lung and gut. The mucosal immune system is charged with the detection and elimination of pathogens while maintaining tolerance toward commensal bacteria and innocuous antigens. The disruption of this delicate balance leads to the development of pathologies affecting the gut, as in the case of inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), celiac diseases or pathologies affecting the respiratory tract as asthma, cystic fibrosis or chronic obstructive pulmonary disease (COPD).
Notwithstanding the fact that epithelial cells play an essential role in the control of mucosal integrity and homeostasis, there is increasing evidence of the important contribution of innate immune cells in these phenomena. For instance, dendritic cells (DCs) play a central role as sentinels of damage or infection by patrolling the mucosal interface. In healthy mucosa, DCs have a tolerogenic phenotype which maintains the homeostasis by activating regulatory T cells. During pathological conditions, DCs perceive the signs of damage through pattern recognition receptors (PRR) and acquire an inflammatory phenotype that allows the activation of both innate and adaptive immune responses. DCs from IBD patients express increased levels of TLR2/TLR4 and co-stimulatory markers allowing them to promote T cell proliferation. Colonic CD103+ DCs, generally associated to tolerance, acquire the ability to release IL-6, IL-12 and TNF- in UC patients. In these conditions, CD103+ DCs do not generate Foxp3+ Treg but induce the differentiation of effector Th1 and Th17 cells. Likewise, in CD patients the production of pro-inflammatory cytokines by colonic DCs correlates with the periods of disease activity. Retinoid acid (RA) is required for optimal Treg induction by intestinal CD103+ DCs in the steady-state but these cells have a reduced expression of RA-generating enzymes in mice with UC. Surprisingly, it was shown that the effects of RA on the immune system depend on the context. In the presence of IL-15, RA induces the release of the pro-inflammatory cytokines IL-12 and IL-23 by DCs promoting intestinal inflammation.
In the lung, allergic asthma is associated with type 2 inflammatory responses. Chronic type 2 airway inflammation can become fibrotic increasing the risk of pulmonary infections or COPD. In addition to their potent immunogenic capacity, DCs can also play a central role in the evolution of tissue damage. DCs are not only activated by infection or injury but also by the complex milieu resulting for other innate cells signals and/or secretions. Neutrophils, eosinophils, basophils, mast cells, iNKT (invariant Natural Killer T cells), MAIT (Mucosal-Associated Invariant T cells), T and ILC (Innate Lymphoid Cells) have a central role in starting tissue damage through DCs activation. Throughout the inflammation, a complex cross-talk exists between these cells via their production of soluble mediators such as histamine, leukotrienes, prostaglandins, cytokines and alarmins.
A combination of approaches including in vitro, ex vivo and animal model-based studies have demonstrated the roles of DCs and the others innate or innate-like T cells cited above in several gut and lung pathologies.
In this Research Topic, we welcome the submission of Original Research, Review and Mini Review articles focusing on, but not limited to, the following subtopics:
1. How soluble mediators released by innate cells disrupt tolerance mechanisms
2. The role of innate cells and inflammatory mediators in gut and lung pathologies
3. Cross-talk between DCs and innate lymphocytes as a trigger of pathology
4. How innate inflammation affects epithelial barrier function inducing damage
Keywords: DENDRITIC CELLS, MUCOSA DISEASES, INFLAMMATORY MEDIATORS, EFFECTOR MECHANISMS, INNATE CELLS
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
