Kidney transplantation is the currently the best mode of treatment for End Stage Renal Disease (ESRD). Although advances in the development of immunosuppressive drugs and of clinical protocols have markedly reduced the incidence and relevance of acute rejection, the outcome of kidney grafts is still significantly influenced by the development of chronic cellular or humoral rejection. In this setting, adaptive alloimmune responses have always been considered as the main, if not the only, player in kidney graft rejection. Consequently, the role of innate immunity in this process has been disregarded for a long period of time. However, in the past two decades, a growing body of evidence has demonstrated that innate immune responses significantly contribute to the priming of the rejection machinery, and control the activation of alloantigen-specific adaptive immunity. Several experimental models of graft rejection in mice have demonstrated that the inhibition of innate immunity not only reduces the incidence of rejection, but can also promote the development of tolerance.
In this scenario, the interplay between antigen-presenting cells such as dendritic cells and T cells is essential. The activation of antigen-presenting cells and the ability to induce a detrimental T cell response against the graft depends upon the priming of cellular and humoral pathways of innate immunity, including (i) the interaction of pattern recognition receptors (PRR) with pathogen-associated molecular patterns (PAMPS) or damage-associated molecular patterns (DAMPS) and (ii) the activation of complement and coagulation cascades. Several factors can induce the activation of innate immune responses in clinical kidney transplantation. In Donation after Brain Death (DBD), brain death itself can promote the systemic production and release of pro-inflammatory cytokines such as monocyte chemotactic peptide 1 (MCP-1) and IL-6. This subsequently leads to the activation of innate immune pathways and cellular responses, such as monocyte recruitment and activation, in several organs including the kidneys. Moreover, warm and cold ischemia during kidney retrieval and preservation followed by reperfusion at the time of transplantation is also known to induce the activation of innate immune responses through several molecular mechanisms including oxidative stress and resident cell apoptosis. This is even more pronounced for Donation after Circulatory Death (DCD), a procedure increasingly used to reduce organ shortage. Interestingly, the communication between innate and adaptive immune responses in kidney graft rejection is bi-directional since there is now clear evidence that adaptive immune response activation may lead to tissue damage through cellular and molecular components of innate immunity.
Taken together, this Research Topic aims to provide a cutting-edge collection of articles that discuss (i) the role of innate immunity activation in the pathogenesis of graft rejection and (ii) the mechanisms of interaction between innate and adaptive immunity in both experimental and clinical kidney transplantation.
We welcome the submission of Original Research articles, Reviews and Mini-Reviews covering, but not limited to, the following sub-topics:
1. Dendritic cell activation in delayed graft function.
2. The role of complement in delayed graft function.
3. Activation of the coagulation cascade: between innate and adaptive response.
4. Non alloantigen-dependent activation of T cells in kidney transplantation.
5. The role of brain death in graft inflammation and subsequent activation of alloimmune response.
6. The role of innate immunity in the antibody-mediated graft damage
7. Innate immunity activation in delayed graft function and long term transplant outcome
8. Complement genetics and acute and chronic graft damage.
9. The role of TLRs in graft injury
10. Dendritic cell-T cell interaction in kidney transplantation: at the border of innate and adaptive immunity.
11. Innate immune response: a novel therapeutic target to prevent or treat kidney graft rejection.
Kidney transplantation is the currently the best mode of treatment for End Stage Renal Disease (ESRD). Although advances in the development of immunosuppressive drugs and of clinical protocols have markedly reduced the incidence and relevance of acute rejection, the outcome of kidney grafts is still significantly influenced by the development of chronic cellular or humoral rejection. In this setting, adaptive alloimmune responses have always been considered as the main, if not the only, player in kidney graft rejection. Consequently, the role of innate immunity in this process has been disregarded for a long period of time. However, in the past two decades, a growing body of evidence has demonstrated that innate immune responses significantly contribute to the priming of the rejection machinery, and control the activation of alloantigen-specific adaptive immunity. Several experimental models of graft rejection in mice have demonstrated that the inhibition of innate immunity not only reduces the incidence of rejection, but can also promote the development of tolerance.
In this scenario, the interplay between antigen-presenting cells such as dendritic cells and T cells is essential. The activation of antigen-presenting cells and the ability to induce a detrimental T cell response against the graft depends upon the priming of cellular and humoral pathways of innate immunity, including (i) the interaction of pattern recognition receptors (PRR) with pathogen-associated molecular patterns (PAMPS) or damage-associated molecular patterns (DAMPS) and (ii) the activation of complement and coagulation cascades. Several factors can induce the activation of innate immune responses in clinical kidney transplantation. In Donation after Brain Death (DBD), brain death itself can promote the systemic production and release of pro-inflammatory cytokines such as monocyte chemotactic peptide 1 (MCP-1) and IL-6. This subsequently leads to the activation of innate immune pathways and cellular responses, such as monocyte recruitment and activation, in several organs including the kidneys. Moreover, warm and cold ischemia during kidney retrieval and preservation followed by reperfusion at the time of transplantation is also known to induce the activation of innate immune responses through several molecular mechanisms including oxidative stress and resident cell apoptosis. This is even more pronounced for Donation after Circulatory Death (DCD), a procedure increasingly used to reduce organ shortage. Interestingly, the communication between innate and adaptive immune responses in kidney graft rejection is bi-directional since there is now clear evidence that adaptive immune response activation may lead to tissue damage through cellular and molecular components of innate immunity.
Taken together, this Research Topic aims to provide a cutting-edge collection of articles that discuss (i) the role of innate immunity activation in the pathogenesis of graft rejection and (ii) the mechanisms of interaction between innate and adaptive immunity in both experimental and clinical kidney transplantation.
We welcome the submission of Original Research articles, Reviews and Mini-Reviews covering, but not limited to, the following sub-topics:
1. Dendritic cell activation in delayed graft function.
2. The role of complement in delayed graft function.
3. Activation of the coagulation cascade: between innate and adaptive response.
4. Non alloantigen-dependent activation of T cells in kidney transplantation.
5. The role of brain death in graft inflammation and subsequent activation of alloimmune response.
6. The role of innate immunity in the antibody-mediated graft damage
7. Innate immunity activation in delayed graft function and long term transplant outcome
8. Complement genetics and acute and chronic graft damage.
9. The role of TLRs in graft injury
10. Dendritic cell-T cell interaction in kidney transplantation: at the border of innate and adaptive immunity.
11. Innate immune response: a novel therapeutic target to prevent or treat kidney graft rejection.