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Dendritic cells and innate immunity in kidney transplantation.

Zhuang Q, Lakkis FG - Kidney Int. (2015)

Bottom Line: First, it highlights the primary role that recipient, rather than donor, DCs have in rejection and reviews their origin and function in the transplanted kidney.Second, it introduces the novel concept that recognition of allogeneic non-self by host monocytes (referred to here as innate allorecognition) is necessary for initiating rejection by inducing monocyte differentiation into mature, antigen-presenting DCs.Both concepts provide opportunities for preventing rejection by targeting monocytes or DCs.

View Article: PubMed Central - PubMed

Affiliation: 1] Thomas E. Starzl Transplantation Institute and the Departments of Surgery, Immunology, and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA [2] Department of Transplantation, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.

ABSTRACT
This review summarizes emerging concepts related to the roles of dendritic cells (DCs) and innate immunity in organ transplant rejection. First, it highlights the primary role that recipient, rather than donor, DCs have in rejection and reviews their origin and function in the transplanted kidney. Second, it introduces the novel concept that recognition of allogeneic non-self by host monocytes (referred to here as innate allorecognition) is necessary for initiating rejection by inducing monocyte differentiation into mature, antigen-presenting DCs. Both concepts provide opportunities for preventing rejection by targeting monocytes or DCs.

No MeSH data available.


Innate allorecognition and danger link innate to adaptive immunity after transplantationRecognition of allogeneic non-self by recipient monocytes is key for generating mature DC that drive graft rejection by T lymphocytes. Danger, which causes inflammation in the graft but is not sufficient for driving rejection, is nevertheless essential for potentiating the adaptive alloimmune response.
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Figure 1: Innate allorecognition and danger link innate to adaptive immunity after transplantationRecognition of allogeneic non-self by recipient monocytes is key for generating mature DC that drive graft rejection by T lymphocytes. Danger, which causes inflammation in the graft but is not sufficient for driving rejection, is nevertheless essential for potentiating the adaptive alloimmune response.

Mentions: By performing heart, kidney, and bone marrow transplants into RAG−/−γc−/− mice, which lack T, B, NK and innate lymphoid cells, we have now established that innate sensing of allogeneic non-self is necessary for initiating alloimmunity 42. In these experiments, allogeneic grafts elicited persistent differentiation of monocytes to mature DC that expressed IL-12 and stimulate T cell proliferation and IFNγ production. In contrast, syngeneic grafts elicited transient and less pronounced differentiation of monocytes to DC, which neither expressed IL-12 nor stimulate IFNγ production. In a heart transplantation model where T cell recognition is restricted to a single foreign antigen on the graft, rejection occurred only if allogeneic non-self was also sensed by the host’s innate immune system. Therefore, danger alone, which is common to both syngeneic and allogeneic grafts, is not sufficient for inducing “full” DC activation. Instead, innate recognition of allogeneic allogeneic non-self by monocytes is required for this process and for initiating T lymphocyte-dependent alloimmunity. These concepts are summarized schematically in Figure 1. The mechanisms by which monocytes recognize allogeneic non-self and the nature of the allodeterminants that trigger monocyte differentiation to mature DC have not been identified yet. Elucidating these mechanisms should provide the possibility of matching between donors and recipients at innate allodeterminants to improve graft outcomes or of interrupting innate allorecognition pathways to prevent acute or chronic rejection.


Dendritic cells and innate immunity in kidney transplantation.

Zhuang Q, Lakkis FG - Kidney Int. (2015)

Innate allorecognition and danger link innate to adaptive immunity after transplantationRecognition of allogeneic non-self by recipient monocytes is key for generating mature DC that drive graft rejection by T lymphocytes. Danger, which causes inflammation in the graft but is not sufficient for driving rejection, is nevertheless essential for potentiating the adaptive alloimmune response.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4382394&req=5

Figure 1: Innate allorecognition and danger link innate to adaptive immunity after transplantationRecognition of allogeneic non-self by recipient monocytes is key for generating mature DC that drive graft rejection by T lymphocytes. Danger, which causes inflammation in the graft but is not sufficient for driving rejection, is nevertheless essential for potentiating the adaptive alloimmune response.
Mentions: By performing heart, kidney, and bone marrow transplants into RAG−/−γc−/− mice, which lack T, B, NK and innate lymphoid cells, we have now established that innate sensing of allogeneic non-self is necessary for initiating alloimmunity 42. In these experiments, allogeneic grafts elicited persistent differentiation of monocytes to mature DC that expressed IL-12 and stimulate T cell proliferation and IFNγ production. In contrast, syngeneic grafts elicited transient and less pronounced differentiation of monocytes to DC, which neither expressed IL-12 nor stimulate IFNγ production. In a heart transplantation model where T cell recognition is restricted to a single foreign antigen on the graft, rejection occurred only if allogeneic non-self was also sensed by the host’s innate immune system. Therefore, danger alone, which is common to both syngeneic and allogeneic grafts, is not sufficient for inducing “full” DC activation. Instead, innate recognition of allogeneic allogeneic non-self by monocytes is required for this process and for initiating T lymphocyte-dependent alloimmunity. These concepts are summarized schematically in Figure 1. The mechanisms by which monocytes recognize allogeneic non-self and the nature of the allodeterminants that trigger monocyte differentiation to mature DC have not been identified yet. Elucidating these mechanisms should provide the possibility of matching between donors and recipients at innate allodeterminants to improve graft outcomes or of interrupting innate allorecognition pathways to prevent acute or chronic rejection.

Bottom Line: First, it highlights the primary role that recipient, rather than donor, DCs have in rejection and reviews their origin and function in the transplanted kidney.Second, it introduces the novel concept that recognition of allogeneic non-self by host monocytes (referred to here as innate allorecognition) is necessary for initiating rejection by inducing monocyte differentiation into mature, antigen-presenting DCs.Both concepts provide opportunities for preventing rejection by targeting monocytes or DCs.

View Article: PubMed Central - PubMed

Affiliation: 1] Thomas E. Starzl Transplantation Institute and the Departments of Surgery, Immunology, and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA [2] Department of Transplantation, The 3rd Xiangya Hospital, Central South University, Changsha, Hunan, China.

ABSTRACT
This review summarizes emerging concepts related to the roles of dendritic cells (DCs) and innate immunity in organ transplant rejection. First, it highlights the primary role that recipient, rather than donor, DCs have in rejection and reviews their origin and function in the transplanted kidney. Second, it introduces the novel concept that recognition of allogeneic non-self by host monocytes (referred to here as innate allorecognition) is necessary for initiating rejection by inducing monocyte differentiation into mature, antigen-presenting DCs. Both concepts provide opportunities for preventing rejection by targeting monocytes or DCs.

No MeSH data available.