Graft-versus-host disease reduces lymph node display of tissue-restricted self-antigens and promotes autoimmunity

Dertschnig, Simone; Evans, Pamela; Sousa, Pedro M.; Manzo, Teresa; Ferrer, Ivana R.; Stauss, Hans J.; Bennett, Clare L.; Chakraverty, Ronjon

doi:10.1172/jci133102

Cited by 31 publications

(49 citation statements)

References 53 publications

(92 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In the setting of mismatched allogeneic stem cell transplantation in mice, onset of graft-versus-host disease can result in CD8 + T cell-mediated destruction of LN FRCs and HEVs and an impaired ability to mount effective humoral immune responses to subsequent infection 104 . Recently, it was shown that graft-versus-host-disease-mediated depletion of LN FRCs results in a decrease of Deaf1-dependent peripheral-tissue-restricted antigen expression, resulting in a loss of peripheral tolerance and an increase in activated autoreactive T cells 105 . These studies highlight the importance of maintaining an intact stromal cell network for effective immunity and for developing and maintaining immune tolerance.…”

Section: Lnsc Participation During Immune Responsesmentioning

confidence: 99%

Lymph node stromal cells: cartographers of the immune system

Krishnamurty¹,

Turley²

2020

Nat Immunol

227

272

View full text Add to dashboard Cite

econdary lymphoid organs (SLOs), including lymph nodes (LNs), spleen and Peyer's patches (PPs), serve as the body's sites of immune cell surveillance. SLOs provide the infrastructure to maintain immune homeostasis and facilitate rapid and effective immune responses. While spleen and PPs serve to filter material in the blood and gastrointestinal tract, respectively, LNs are strategically situated in proximity to lymphatic and vascular branching points to effectively filter antigens and facilitate immune cell entry from surrounding tissues. Pioneering studies of human lymphoid organ development from the 1970s revealed that humans possess hundreds of lymph nodes variably positioned throughout the body, whereas mice have 22 LNs that always develop in the same distinct body sites 1-3. The hallmark feature of SLOs is the highly ordered compartmentalization of T cells, B cells and myeloid cells to generate optimal antigen-specific adaptive immune responses. Non-hematopoietic lymph node stromal cells (LNSCs), made up of both mesenchymal and endothelial cells, are paramount to maintaining LN integrity and function. LNSCs play a key role in LN organogenesis, maintenance of LN cellularity and compartmentalization and supporting immune responses. In this review, we will address recent advances elucidating the contribution of LNSCs, primarily mesenchymal cells, during immune system development and immune responses in adulthood, and highlight ongoing work that aims to expand our understanding of the heterogeneity that exists among LNSCs. LNSC coordination of LN organogenesis LN organogenesis begins as early as embryonic day (E)12.5-E13.5 in mice and weeks 8-11 of gestation in humans via the interactions of two key cell types, lymphoid tissue inducer (LTi) cells and lymphoid tissue organizer (LTo) cells, which, when brought together, form the primordial LN anlagen 1,4. LTi cells, belonging to the family of innate lymphoid cells (ILCs), originate from hematopoietic CD45 + Lin-IL-7Rα + Sca1 lo c-Kit lo common lymphoid progenitors (CLPs) in the mouse fetal liver and differentiate via expression of the transcription factors Id2 and RORγt. Mice deficient in Id2 or Rorγt are devoid of LTi cells and consequently lack LNs, highlighting the importance of LTi cells in this process 5,6. Differentiated LTi cells, also categorized as group 3 ILCs, are CD45 + CD3-RORγt + cells and are further defined by their expression of IL-7Rα, integrin α4β7, receptor activator of NF-κB (RANK) and its ligand RANKL, lymphotoxin-α1β2 (LT)

show abstract

Section: Lnsc Participation During Immune Responsesmentioning

confidence: 99%

Lymph node stromal cells: cartographers of the immune system

Krishnamurty¹,

Turley²

2020

Nat Immunol

227

272

View full text Add to dashboard Cite

show abstract

“…A doença é mediada pelos linfócitos T do enxerto, que atacam órgãos e tecidos do receptor. [2][3] Na DECH aguda, alguns órgãos podem ser acometidos, como pele, fígado e Trato Gastrointestinal (TGI). Já a DECH crônica é uma das principais causas tardias de morbimortalidade do TCTH alogênico, em que as manifestações clínicas podem ser restritas a um único órgão ou disseminadas, com profundo impacto na qualidade de vida, uma vez que a fisiopatologia envolve inflamação, imunidade celular e humoral e fibrose.…”

Section: Resúmenunclassified

“…Já a DECH crônica é uma das principais causas tardias de morbimortalidade do TCTH alogênico, em que as manifestações clínicas podem ser restritas a um único órgão ou disseminadas, com profundo impacto na qualidade de vida, uma vez que a fisiopatologia envolve inflamação, imunidade celular e humoral e fibrose. [2][3] O acometimento da DECH é complexo e pode ser estressante para o paciente, o familiar e a equipe de saúde, uma vez que a complicação possui impacto sobre a rotina de vida do paciente, deteriorando a qualidade de vida deste, tanto nos aspectos físicos quanto sociais e emocionais.…”

Section: Resúmenunclassified

“…(hepatite e icterícia) e trato gastrointestinal (dor abdominal, náusea, diarreia e até mesmo sangramento intestinal). [3][4] Após o aparecimento desses sintomas, deve haver o início do tratamento com o uso de corticosteroides, desta forma, há aumento na imunossupressão desse paciente, favorecendo o aparecimento de infecções, tanto bacterianas, como virais e fúngicas. Nesses mesmos estudos, outros cuidados mencionados foram: avalição física; prevenção de infecção; prevenção de quedas; controle de energia; redução de ansiedade; terapias de relaxamento; assistência ao autocuidado; terapia nutricional; cuidados com o ambiente; cuidados com a terapia medicamentosa; e controle da diarreia.…”

Section: Processo De Enfermagemunclassified

See 1 more Smart Citation

Cuidados De Enfermagem Ao Paciente Com Doença Enxerto Contra Hospedeiro

Cordeiro

Rodrigues

Piubello

et al. 2021

Rev enferm UFPE on line.

View full text Add to dashboard Cite

Objetivo: analisar as evidências disponíveis sobre os cuidados de enfermagem realizados ao paciente em pós-Transplante de Células-Tronco Hematopoiéticas com Doença Enxerto Contra Hospedeiro. Método: revisão integrativa com a busca de estudos primários em seis bases de dados na área da saúde e uma biblioteca virtual em saúde. Foi utilizada estratégia de busca ampla e incluíram-se as pesquisas publicadas em inglês, português ou espanhol, entre 2014 e 2018. Assim, a amostra da revisão foi composta por oito estudos primários. Resultados: para organizar a síntese de conhecimento, os estudos foram agrupados em três categorias: processo de enfermagem (n=4), impacto do transplante (n=2) e tecnologias para o cuidado (n=2). Conclusão: os estudos abordam o cuidado de enfermagem de forma integrada a outras complicações, não abordando a doença do enxerto especificamente. Pontuou-se o uso da sistematização da assistência de enfermagem, custos com o tratamento, dimensionamento da equipe de enfermagem e uso de tecnologias como estratégias para realização do cuidado. As evidências geradas são incipientes e apontam para a necessidade do desenvolvimento de mais estudos na área.

show abstract

“…The disruption of TRC networks subsequently damages T cell organization and T cell-dependent humoral responses [ 81 ]. Moreover, during GVHD, LN FRCs downregulate DEAF-1, an autoimmune regulator-like transcription factor required for the expression of several TRAs, leading to a breakdown of peripheral tolerance mechanisms dependent on TRA expression by SCs and promoting autoimmune disease development in BM-transplanted mice [ 82 ].…”

Section: Lnscs Modulate Alloreactive T Cell Activation Following Tmentioning

confidence: 99%

Lymph Node Stromal Cells: Mapmakers of T Cell Immunity

Harlé

Kowalski

Garnier

et al. 2020

IJMS

View full text Add to dashboard Cite

Stromal cells (SCs) are strategically positioned in both lymphoid and nonlymphoid organs to provide a scaffold and orchestrate immunity by modulating immune cell maturation, migration and activation. Recent characterizations of SCs have expanded our understanding of their heterogeneity and suggested a functional specialization of distinct SC subsets, further modulated by the microenvironment. Lymph node SCs (LNSCs) have been shown to be particularly important in maintaining immune homeostasis and T cell tolerance. Under inflammation situations, such as viral infections or tumor development, SCs undergo profound changes in their numbers and phenotype and play important roles in contributing to either the activation or the control of T cell immunity. In this review, we highlight the role of SCs located in LNs in shaping peripheral T cell responses in different immune contexts, such as autoimmunity, viral and cancer immunity.

show abstract

Graft-versus-host disease reduces lymph node display of tissue-restricted self-antigens and promotes autoimmunity

Cited by 31 publications

References 53 publications

Lymph node stromal cells: cartographers of the immune system

Lymph node stromal cells: cartographers of the immune system

Cuidados De Enfermagem Ao Paciente Com Doença Enxerto Contra Hospedeiro

Lymph Node Stromal Cells: Mapmakers of T Cell Immunity

Contact Info

Product

Resources

About