scholarly journals Role of C1q in Efferocytosis and Self-Tolerance — Links With Autoimmunity

10.5772/60519 ◽  
2015 ◽  
Author(s):  
Philippe Frachet ◽  
Pascale Tacnet-Delorme ◽  
Christine Gaboriaud ◽  
Nicole M. Thielens
Keyword(s):  
Self Tolerance

Deciphering the Role of microRNAs in Regulation of Immune Surveillance, Self-Tolerance and Allograft Transplant Outcome

2018 ◽  
Vol 13 (5) ◽  
pp. 336-344
Author(s):  
Cherry S. Leung ◽  
Song Lu ◽  
Jiatao Li ◽  
William KK Wu ◽  
Kathy O. Lui
Keyword(s):  
Immune Surveillance ◽  
Transplant Outcome ◽  
Self Tolerance

scholarly journals Induction of autoreactive B cells allows priming of autoreactive T cells.

1991 ◽  
Vol 173 (6) ◽  
pp. 1433-1439 ◽  
Author(s):  
R H Lin ◽  
M J Mamula ◽  
J A Hardin ◽  
C A Janeway
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cytochrome C ◽  
Autoantibody Production ◽  
Autoreactive T Cells ◽  
Human Cytochrome ◽  
Self Tolerance ◽  
Human Cytochrome C

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.

scholarly journals CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Trinidad Hernández-Caselles ◽  
Rubén Corral-San Miguel ◽  
Antonio José Ruiz-Alcaraz ◽  
Pilar García-Peñarrubia
Keyword(s):  
Nk Cells ◽  
Innate Immune ◽  
Inhibitory Receptor ◽  
Inhibitory Function ◽  
Activating Receptors ◽  
Self Tolerance ◽  
Lower Extent ◽  
Low Cytotoxicity ◽  
High Cytotoxicity

CD33 (siglec-3), a well-known target in leukemia therapy, is an inhibitory sialoadhesin expressed in human leukocytes of the myeloid lineage and some lymphoid subsets, including NK cells. It may constitute a control mechanism of the innate immune system; nevertheless, its role as an inhibitory receptor remains elusive. Using human NK cells as a cellular model, we analyzed CD33 inhibitory function upon different activating receptors. In high-cytotoxicity NKL cells, CD33 displayed a prominent inhibition on cytotoxicity triggered by the activating receptors NKG2D and, in a lower extent, 2B4, whereas it did not inhibit NKp46-induced cytotoxicity. NKp46 was partially inhibited by CD33 only when low-cytotoxicity NKL cells were tested. CD33 triggering did not inhibit IFN-γsecretion, contrasting with ILT-2 and CD94/NKG2A inhibitory receptors that inhibited cytotoxicity and IFN-γsecretion induced by all activating receptors tested. CD33-mediated inhibition of NKG2D-induced triggering involved Vav1 dephosphorylation. Our results support the role of CD33 as an inhibitory receptor preferentially regulating the NKG2D/DAP10 cytotoxic signaling pathway, which could be involved in self-tolerance and tumor and infected cell recognition.

scholarly journals AIRE Functions As an E3 Ubiquitin Ligase

2004 ◽  
Vol 199 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Daisuke Uchida ◽  
Shigetsugu Hatakeyama ◽  
Akemi Matsushima ◽  
Hongwei Han ◽  
Satoshi Ishido ◽  
...  
Keyword(s):  
E3 Ligase ◽  
Autosomal Recessive Inheritance ◽  
Missense Mutations ◽  
The Novel ◽  
Aire Gene ◽  
Enzymatic Function ◽  
Self Tolerance ◽  
Organ Specific ◽  
Proteasome Pathway

Autoimmune regulator (AIRE) gene mutation is responsible for the development of autoimmune-polyendocrinopathy-candidiasis ectodermal dystrophy, an organ-specific autoimmune disease with monogenic autosomal recessive inheritance. AIRE is predominantly expressed in medullary epithelial cells of the thymus and is considered to play important roles in the establishment of self-tolerance. AIRE contains two plant homeodomain (PHD) domains, and the novel role of PHD as an E3 ubiquitin (Ub) ligase has just emerged. Here we show that the first PHD (PHD1) of AIRE mediates E3 ligase activity. The significance of this finding was underscored by the fact that disease-causing missense mutations in the PHD1 (C311Y and P326Q) abolished its E3 ligase activity. These results add a novel enzymatic function for AIRE and suggest an indispensable role of the Ub proteasome pathway in the establishment of self-tolerance, in which AIRE is involved.

scholarly journals Essential role of CCL21 in establishment of central self-tolerance in T cells

2017 ◽  
Vol 214 (7) ◽  
pp. 1925-1935 ◽  
Author(s):  
Mina Kozai ◽  
Yuki Kubo ◽  
Tomoya Katakai ◽  
Hiroyuki Kondo ◽  
Hiroshi Kiyonari ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Essential Role ◽  
Functional Inequality ◽  
Cell Accumulation ◽  
Self Tolerance ◽  
Thymic Medulla ◽  
Deficient Mice

The chemokine receptor CCR7 directs T cell relocation into and within lymphoid organs, including the migration of developing thymocytes into the thymic medulla. However, how three functional CCR7 ligands in mouse, CCL19, CCL21Ser, and CCL21Leu, divide their roles in immune organs is unclear. By producing mice specifically deficient in CCL21Ser, we show that CCL21Ser is essential for the accumulation of positively selected thymocytes in the thymic medulla. CCL21Ser-deficient mice were impaired in the medullary deletion of self-reactive thymocytes and developed autoimmune dacryoadenitis. T cell accumulation in the lymph nodes was also defective. These results indicate a nonredundant role of CCL21Ser in the establishment of self-tolerance in T cells in the thymic medulla, and reveal a functional inequality among CCR7 ligands in vivo.

scholarly journals The Histone Modification Code in the Pathogenesis of Autoimmune Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yasuto Araki ◽  
Toshihide Mimura
Keyword(s):  
Autoimmune Diseases ◽  
Histone Modifications ◽  
Lupus Erythematosus ◽  
Cell Types ◽  
Biliary Cirrhosis ◽  
Loss Of Self ◽  
Self Tolerance ◽  
Different Cell Types

Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes.

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