Vinay S. Mahajan
Brigham and Women's Hospital
Immunoglobulin ECytotoxic T cellAntibodyCD8ChemistryT-cell receptorImmunologyMajor histocompatibility complexT cellDiseaseSialic acidIgG4-related diseaseFibrosisImmunoglobulin GPopulationMedicineBiologyImmune systemCell biology
58Publications
23H-index
2,445Citations
Publications 53
Newest
#1Vinay S. Mahajan (Brigham and Women's Hospital)H-Index: 23
#2Hamid Mattoo (Ragon Institute of MGH, MIT and Harvard)H-Index: 21
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 11 authors...
The B1 and B2 lineages of B cells contribute to protection from pathogens in distinct ways. The role of the DNA CpG methylome in specifying these two B-cell fates is still unclear. Here we profile the CpG modifications and transcriptomes of peritoneal B1a and follicular B2 cells, as well as their respective proB cell precursors in the fetal liver and adult bone marrow from wild-type and CD19-Cre Dnmt3a floxed mice lacking DNMT3A in the B lineage. We show that an underlying foundational CpG methy...
Source
#1Naoki Kaneko (Ragon Institute of MGH, MIT and Harvard)H-Index: 10
#2Julie Boucau (Ragon Institute of MGH, MIT and Harvard)H-Index: 7
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 19 authors...
The contributions of T cells infiltrating the lungs to SARS-CoV-2 clearance and disease progression are poorly understood. Although studies of CD8+ T cells in bronchoalveolar lavage and blood have suggested that these cells are exhausted in severe COVID-19, CD4+ T cells have not been systematically interrogated within the lung parenchyma. We establish here that cytotoxic CD4+ T cells (CD4+CTLs) are prominently expanded in the COVID-19 lung infiltrate. CD4+CTL numbers in the lung increase with di...
Source
#2Faisal AlsufyaniH-Index: 2
Last. Shiv PillaiH-Index: 50
view all 10 authors...
Although fibrotic disorders are frequently assumed to be linked to TH2 cells, quantitative tissue interrogation studies have rarely been performed to establish this link and certainly many fibrotic diseases do not fall within the type 2/allergic disease spectrum. We have previously linked two human autoimmune fibrotic diseases, IgG4-related disease and systemic sclerosis, to the clonal expansion and lesional accumulation of CD4+CTLs. In both these diseases TH2 cell accumulation was found to be s...
1 CitationsSource
#1Cory A. Perugino (Harvard University)H-Index: 13
#2Naoki Kaneko (Kyushu University)H-Index: 10
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 28 authors...
Abstract Background IgG4-related disease (IgG4-RD) is an immune-mediated fibrotic disorder that has been linked to CD4+ cytotoxic T lymphocytes (CD4+CTLs). The effector phenotype of CD4+CTLs, the relevance of both CD8+ cytotoxic T lymphocytes (CD8+CTLs) and of apoptotic cell death remain undefined in IgG4-RD. Objective The goals of this study were to define CD4+CTL heterogeneity, characterize the CD8+CTL response in the blood and in lesions, and determine whether enhanced apoptosis may contribut...
9 CitationsSource
#1Naoki Kaneko (Ragon Institute of MGH, MIT and Harvard)H-Index: 10
#2Hsiao-Hsuan Kuo (Ragon Institute of MGH, MIT and Harvard)H-Index: 5
view all 51 authors...
Humoral responses in coronavirus disease 2019 (COVID-19) are often of limited durability, as seen with other human coronavirus epidemics. To address the underlying etiology, we examined post mortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers and a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells. Absence of germinal centers correlated with an early specific block in Bcl-6+ TFH cell differentiatio...
161 CitationsSource
#1Naoki Kaneko (Ragon Institute of MGH, MIT and Harvard)H-Index: 10
#2Hsiao-Hsuan Kuo (Ragon Institute of MGH, MIT and Harvard)H-Index: 5
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 50 authors...
Humoral responses in COVID-19 disease are often of limited durability, as seen with other human coronavirus epidemics To address the underlying etiology, we examined postmortem thoracic lymph nodes and spleens in acute SARS-CoV-2 infection and observed the absence of germinal centers, a striking reduction in Bcl-6+ germinal center B cells but preservation of AID+ B cells Absence of germinal centers correlated with an early specific block in Bcl-6+TFH cell differentiation together with an increas...
13 CitationsSource
#1Takashi MaeharaH-Index: 20
#2Naoki Kaneko (MIT: Massachusetts Institute of Technology)H-Index: 10
Last. Shiv Pillai (MIT: Massachusetts Institute of Technology)H-Index: 50
view all 16 authors...
Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of thirty-five untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and...
23 CitationsSource
#1Vinay S. Mahajan (Ragon Institute of MGH, MIT and Harvard)H-Index: 23
#2Hamid Mattoo (Ragon Institute of MGH, MIT and Harvard)H-Index: 21
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 11 authors...
We show that DNA methylation is a layered process in B lymphocytes. An underlying foundational methylome is stably established during B lineage commitment and overlaid with a DNMT3A-maintained dynamic methylome which is sculpted in distinct ways in B1 and B2 B cells during B cell development. An engineered loss of DNMT3A after commitment to the B lineage unmasks a foundational methylome that is shared in both B1 and B2 sub-lineages. The dynamic methylome is comprised of novel enhancers whose met...
Source
#1Sandra Diaz (UCSD: University of California, San Diego)H-Index: 31
#2Yang Ji (UCSD: University of California, San Diego)
Last. Ajit Varki (UCSD: University of California, San Diego)H-Index: 111
view all 7 authors...
Source
#1Emanuel Della-Torre (UniSR: Vita-Salute San Raffaele University)H-Index: 25
#2Elena Rigamonti (UniSR: Vita-Salute San Raffaele University)H-Index: 9
Last. Shiv Pillai (Ragon Institute of MGH, MIT and Harvard)H-Index: 50
view all 19 authors...
Background IgG4-related disease (IgG4-RD) is a fibroinflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. Objective In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in patients with IgG4-RD. Methods Total circulating CD19+ B lymphocytes, naive B cells, memory B cells, or plasmablasts from pati...
25 CitationsSource