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Immune function of epithelial cells
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Richard S. Blumberg, Wayne Lencer, Arthur Kaser, Jerrold R. Turner
Epithelial cells not only determine cell fate decisions in mucosal T cells via their actions on DCs, they also regulate IgG/IgA class switching in the B-cell compartment at mucosal surfaces. Epithelial cells lining tonsillar crypts form pockets that contain B cells actively performing class switching at that locale. When these epithelial cells sense microbial components via TLRs, they release soluble mediators such as B-cell activating factor (BAFF, encoded by TNFSF13B) that induce class switching through the induction of activation-induced cytidine deaminase (AID). This epithelial-cell-induced class switching is amplified by TSLP by means of a route that involves the “licensing” function of DCs. Remarkably, epithelial cells also secrete an inhibitor of this process, secretory leukocyte protease inhibitor, which inhibits AID function in B cells. A similar process is operative in the intestine, where bacteria induce the cytokine APRIL (a proliferation-inducing ligand, encoded by TNFSF13) in the epithelium and thereby induce T-cell independent IgA and IgG class switching.
Non-Hodgkin Lymphoma
Published in Tariq I. Mughal, Precision Haematological Cancer Medicine, 2018
Most mature B-cell lymphomas are derived from B-cells within the germinal centre (GC) of the lymphoid follicle; rarely in the case of composite lymphomas is it defined by the presence of two different histologic subtypes. The cell of origin tends to be a pluripotential stem cell rather than a precursor committed or a mature cell. Considerably less is known about mature T-cell and NK-cell lymphomas, which are derived from the immune cells, some of which can be antigen-specific, for example CD4- and CD-8 positive T-cells, whilst others, such as γδT-cells, are not. The clinical importance of the precise biological and genetic make-up, as well as the tumour macro- and micro-environment composition, the immune cells, fibrosis and angiogenesis, are now increasingly recognized to affect the prognosis and survival, as well as the impact treatment. Distinctive chromosomal translocations, numerical or structural, are associated with most lymphomas. Both B-cells and T-cells usually undergo rearrangement of their antigen receptor genes, involving immunoglobulin genes or T-cell receptor (TCR), respectively. These are useful to confirm clonality. Frequent chromosomal translocations are often implicated in the process of lymphomagenesis. For example, about 85% of patients with FL have a t(14;18) translocation, which causes the juxtaposition of the BCL2 gene on chromosome 18 to the transcriptionally active IGH region on chromosome 14 (Figures 11.2, 11.3 and 11.4). Similarly, in patients with BL, a simple translocation involving the MYC gene on chromosome 8 and the IGH gene on chromosome 14, occurs in 80–90% of cases. PVT1 gene, thought to result in increased MYC expression in addition to the IGH-driven increase in expression, is also involved in some cases (Figures 11.5 and 11.6). MYC translocations can also occur in about 10% DLBCL and confers an unfavourable prognosis, and when associated with BCL2 or, less often to BCL6, results in the so-called ‘double-hit’, ‘triple-hit’ or ‘double-protein expression’ lymphomas, now collectively termed ‘high-grade B-cell lymphomas’ (HGBL) (Figure 11.7). Interestingly, the spectrum of MYC mutations and their impact on clinical outcomes is quite diverse; unlike MYC gene translocations and over-expression, MYC gene mutations per se, do not appear to have an important driver role in DLBCL. The BCL6 proto-oncogene encodes a transcriptional repressor that is required for the GCB cell development and plays a driver role in lymphomagenesis; BCL6 may also be regulated by the FBX011 gene, the loss of which has now also been implicated in lymphomagenesis. Very rarely do unique IGH rearrangements play a potential role, for example IGH-TNFSF13 and t(14;15)(q32;q11) in DLBCL, and IGH-CCND3 in other lymphomas.
Plasma pro- and anti-inflammatory cytokines may relate to cocaine use, cognitive functioning, and depressive symptoms in cocaine use disorder
Published in The American Journal of Drug and Alcohol Abuse, 2021
Sydney N. Stamatovich, Paula Lopez-Gamundi, Robert Suchting, Gabriela D. Colpo, Consuelo Walss-Bass, Scott D. Lane, Joy M. Schmitz, Margaret C. Wardle
Elastic net analysis identified four predominantly pro-inflammatory cytokines as related to frequency of cocaine use: IL-29, scD163, Eotaxin-1 CCL11, and APRIL/TNFSF13. However, only APRIL/TNSFS13 positively related to cocaine use, consistent with our hypothesis. APRIL/TNFSF13 is part of the TNF superfamily and plays a role in proliferation of tumor cells. Some research suggests that APRIL/TNFSFS13 is increased in schizophrenia (61). However, there is little literature regarding APRIL/TNFSFS13 in substance use. Thus, it was unanticipated that APRIL/TNFSFS13 would relate to cocaine use, although the direction of this relationship is broadly in line with our hypotheses.
The BAFF / APRIL system as therapeutic target in multiple sclerosis
Published in Expert Opinion on Therapeutic Targets, 2020
Roberta Magliozzi, Damiano Marastoni, Massimiliano Calabrese
BAFF (also known as BLyS, TALL-1, THANK, TNFSF13B, CD257 and zTNF4) and APRIL (TNFSF13, CD256), a structural homologue of BAFF, are type II transmembrane proteins of the tumor necrosis factor (TNF) cytokine superfamily [12–14].
Investigating Mechanisms of Response or Resistance to Immune Checkpoint Inhibitors by Analyzing Cell-Cell Communications in Tumors Before and After Programmed Cell Death-1 (PD-1) Targeted Therapy: An Integrative Analysis Using Single-cell RNA and Bulk-RNA Sequencing Data
Published in OncoImmunology, 2021
Yi-Quan Jiang, Zi-Xian Wang, Ming Zhong, Lu-Jun Shen, Xue Han, Xuxiazi Zou, Xin-Yi Liu, Yi-Nan Deng, Yang Yang, Gui-Hua Chen, Wuguo Deng, Jin-Hua Huang
SELP/SELL/SELE-SELPLG interactions became relatively stronger in nonresponders; among them, SELE-SELPLG interactions between endothelial cells and T cells/pDCs/plasma cells were drastically relatively upregulated in nonresponders versus responders. TNFSF10/MIF-TNFRSF10D interactions between other cells and endothelial cells and TNFSF13-related ligand-receptor interactions between pDCs/macrophages and other cells were consistently weaker in responders than in nonresponders. AREG-EGFR interactions between macrophages/pDCs/NK cells/tumor cells and CAFs/tumor cells, TGFB1-EGFR interactions between tumor cells and activated CD8 T cells/exhausted CD8 T cells, COPA-EGFR interactions between tumor cells and exhausted CD8 T cells/memory CD8 T cells were relatively weaker in responders than in nonresponders. CXCL12-CXCR3/CXCR4/CXCR7(ACKR3)/DPP4 interactions were consistently downregulated in responders but upregulated in nonresponders; among them, CXCL12-CXCR3/CXCR4/CXCR7 interactions were mainly observed between CAFs/endothelial cells and other cells, and CXCL12-DPP4 interactions were observed between CAFs and CAFs/T cells/tumor cells. CCL5-CCR5/CCR4 interactions between T cells/NK cells and T cells/endothelial cells were upregulated in both responders and nonresponders, but the increases were sharper in nonresponders; CCL5-CCR4 interactions between exhausted CD8 T cells/NK cells and CD4 T cells/Tregs/proliferative T cells were significantly stronger in nonresponders than in responders. CD74-MIF/COPA/APP interactions were significantly downregulated in responders and upregulated in nonresponders. CD74-MIF/COPA/APP interactions were slightly upregulated between B cells/DCs and other cells and were drastically upregulated between macrophages and other cells in nonresponders versus responders. CD55-ADGRE5 interactions were broadly downregulated between several kinds of cells and B cells/CD8 T cells/NK cells/proliferative T cells but upregulated between other immune cells and tumor cells in responders; however, in nonresponders, they showed a different pattern. LGALS9-related ligand-receptor interactions between DCs/endothelial cells/macrophages/pDCs and other cells were relatively stronger in nonresponders than responders, while LGALS9-CD44 interactions were weaker.