Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling

The immune system mediates tissue responses under both physiological and pathological conditions, impacting the inflammatory, fibrogenic and regenerative components. In addition to various leukocyte subsets, it is now recognized that epithelial, endothelial and other non-hematopoietic tissue cell ty...

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Prif Awduron: Linda C. Burkly, John Silke, Timothy S. Zheng
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author Linda C. Burkly
John Silke
Timothy S. Zheng
author_browse John Silke
Linda C. Burkly
Timothy S. Zheng
author_facet Linda C. Burkly
John Silke
Timothy S. Zheng
author_sort Linda C. Burkly
collection Directory of Open Access Books
description The immune system mediates tissue responses under both physiological and pathological conditions, impacting the inflammatory, fibrogenic and regenerative components. In addition to various leukocyte subsets, it is now recognized that epithelial, endothelial and other non-hematopoietic tissue cell types actively contribute to the interplay shaping tissue responses. Further understanding the molecular pathways and mechanisms mediating these tissue responses is of great interest. In the past decade, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, FGF-inducible molecule-14 (Fn14), members of the TNF/TNFR superfamily, have emerged as a prominent molecular axis regulating tissue responses. Generally leukocyte-derived, TWEAK signals through Fn14 which is highly induced in injured and diseased tissues on the surface of parenchymal, stromal and progenitor cells, thereby orchestrating a host of tissue-shaping responses, including inflammation, angiogenesis, cell proliferation or death, and the regulation of progenitor cells. Compelling preclinical results indicate that whereas transient TWEAK/Fn14 activation promotes productive tissue responses after acute injury, excessive or persistent TWEAK/Fn14 activation drives pathological tissue responses, leading to progressive damage and degeneration in target organs of injury, autoimmune and inflammatory diseases and cancer. Given that the highly inducible pattern of Fn14 expression is well conserved between mouse and man, the role of TWEAK/Fn14 in human disease is an area of intense investigation. Recent findings have also begun to shed light on how the TWEAK/Fn14 pathway fits into the immune network, interplaying with other well-established pathways, including TNFa, IL-17, IL-13 and TGFb, in regulating tissue responses. The noncanonical nuclear factor kB (NF?B) pathway plays a role in immunity and disease pathologies and appears to be activated by only a subset of TNF/ TNFR superfamily members. Of the various signaling pathways downstream of TWEAK/Fn14, particular attention has been placed on the noncanonical NF?B pathway given that given that TWEAK induces acute activation of canonical NF?B but prolonged activation of noncanonical pathway. Thus dovetailing of the TWEAK/Fn14 axis with noncanonical NF?B pathway activation may be a key mechanism underlying tissue responses. Also of great interest is a deeper understanding of where, when and how tissue responses are regulated by other TNF/ TNFR superfamily members that can signal through noncanonical NF?B. This Research Topic issue will cover: 1. TWEAK/Fn14 pathway biology, role in tissue responses, injury, and disease pathogenesis 2. Role of noncanonical NFkB signaling cascade in tissue responses 3. Translational studies of relevance of TWEAK/Fn14 and noncanonical NFkB in human disease 4. Other TNF superfamily members’ signaling through noncanonical NFkB in the regulation of tissue responses 5. Reviews and Perspectives on the above
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spelling doab-20.500.12854ir-580412024-03-31T13:09:55Z Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling Linda C. Burkly John Silke Timothy S. Zheng R5-920 RC581-607 CD40 BAFFR TWEAK TNFR2 Fn14 Rank NFkB LTbR Noncanonical thema EDItEUR::M Medicine and Nursing The immune system mediates tissue responses under both physiological and pathological conditions, impacting the inflammatory, fibrogenic and regenerative components. In addition to various leukocyte subsets, it is now recognized that epithelial, endothelial and other non-hematopoietic tissue cell types actively contribute to the interplay shaping tissue responses. Further understanding the molecular pathways and mechanisms mediating these tissue responses is of great interest. In the past decade, TNF-like weak inducer of apoptosis (TWEAK) and its receptor, FGF-inducible molecule-14 (Fn14), members of the TNF/TNFR superfamily, have emerged as a prominent molecular axis regulating tissue responses. Generally leukocyte-derived, TWEAK signals through Fn14 which is highly induced in injured and diseased tissues on the surface of parenchymal, stromal and progenitor cells, thereby orchestrating a host of tissue-shaping responses, including inflammation, angiogenesis, cell proliferation or death, and the regulation of progenitor cells. Compelling preclinical results indicate that whereas transient TWEAK/Fn14 activation promotes productive tissue responses after acute injury, excessive or persistent TWEAK/Fn14 activation drives pathological tissue responses, leading to progressive damage and degeneration in target organs of injury, autoimmune and inflammatory diseases and cancer. Given that the highly inducible pattern of Fn14 expression is well conserved between mouse and man, the role of TWEAK/Fn14 in human disease is an area of intense investigation. Recent findings have also begun to shed light on how the TWEAK/Fn14 pathway fits into the immune network, interplaying with other well-established pathways, including TNFa, IL-17, IL-13 and TGFb, in regulating tissue responses. The noncanonical nuclear factor kB (NF?B) pathway plays a role in immunity and disease pathologies and appears to be activated by only a subset of TNF/ TNFR superfamily members. Of the various signaling pathways downstream of TWEAK/Fn14, particular attention has been placed on the noncanonical NF?B pathway given that given that TWEAK induces acute activation of canonical NF?B but prolonged activation of noncanonical pathway. Thus dovetailing of the TWEAK/Fn14 axis with noncanonical NF?B pathway activation may be a key mechanism underlying tissue responses. Also of great interest is a deeper understanding of where, when and how tissue responses are regulated by other TNF/ TNFR superfamily members that can signal through noncanonical NF?B. This Research Topic issue will cover: 1. TWEAK/Fn14 pathway biology, role in tissue responses, injury, and disease pathogenesis 2. Role of noncanonical NFkB signaling cascade in tissue responses 3. Translational studies of relevance of TWEAK/Fn14 and noncanonical NFkB in human disease 4. Other TNF superfamily members’ signaling through noncanonical NFkB in the regulation of tissue responses 5. Reviews and Perspectives on the above 2021-02-12T01:31:14Z 2021-02-12T01:31:14Z 2016-04-07 11:22:02 2016 book 18824 16648714 9782889197002 https://directory.doabooks.org/handle/20.500.12854/58041 eng Frontiers Research Topics image/jpeg Attribution 4.0 International http://www.frontiersin.org/books/Regulation_of_Tissue_Responses_The_TWEAK_Fn14_Pathway_and_other_TNF_TNFR_Superfamily_Members_that_A/773 http://journal.frontiersin.org/researchtopic/1413/regulation-of-tissue-responses-the-tweakfn14-pathway-and-other-tnf-tnfr-superfamily-members-that-act Frontiers Media SA 10.3389/978-2-88919-700-2 10.3389/978-2-88919-700-2 bf5ce210-e72e-4860-ba9b-c305640ff3ae 9782889197002 201 open access
spellingShingle R5-920
RC581-607
CD40
BAFFR
TWEAK
TNFR2
Fn14
Rank
NFkB
LTbR
Noncanonical
thema EDItEUR::M Medicine and Nursing
Linda C. Burkly
John Silke
Timothy S. Zheng
Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling
title Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling
title_full Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling
title_fullStr Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling
title_full_unstemmed Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling
title_short Regulation of Tissue Responses: The TWEAK/Fn14 Pathway and other TNF/ TNFR Superfamily Members that Activate Noncanonical NFkB Signaling
title_sort regulation of tissue responses the tweak fn14 pathway and other tnf tnfr superfamily members that activate noncanonical nfkb signaling
topic R5-920
RC581-607
CD40
BAFFR
TWEAK
TNFR2
Fn14
Rank
NFkB
LTbR
Noncanonical
thema EDItEUR::M Medicine and Nursing
topic_facet R5-920
RC581-607
CD40
BAFFR
TWEAK
TNFR2
Fn14
Rank
NFkB
LTbR
Noncanonical
thema EDItEUR::M Medicine and Nursing
url 18824
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