Publications by authors named "Faisal Alsufyani"

6 Publications

  • Page 1 of 1

CD4CTLs in Fibrosing Mediastinitis Linked to .

J Immunol 2021 02 16;206(3):524-530. Epub 2020 Dec 16.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;

Although fibrotic disorders are frequently assumed to be linked to T 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 CD4CTLs. In both these diseases T cell accumulation was found to be sparse. Fibrosing mediastinitis linked to infection histologically resembles IgG4-related disease in terms of the inflammatory infiltrate and fibrosis, and it provides an example of a fibrotic disease of infectious origin in which the potentially profibrotic T cells may be induced and reactivated by fungal Ags. We show in this study that, in this human disease, CD4CTLs accumulate in the blood, are clonally expanded, infiltrate into disease lesions, and can be reactivated in vitro by Ags. T cells are relatively sparse at lesional sites. These studies support a general role for CD4CTLs in inflammatory fibrosis and suggest that fibrosing mediastinitis is an Ag-driven disease that may provide important mechanistic insights into the pathogenesis of idiopathic fibrotic diseases.
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http://dx.doi.org/10.4049/jimmunol.2000433DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7978153PMC
February 2021

DOCK2 Sets the Threshold for Entry into the Virtual Memory CD8 T Cell Compartment by Negatively Regulating Tonic TCR Triggering.

J Immunol 2020 01 18;204(1):49-57. Epub 2019 Nov 18.

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139;

The control of cytoskeletal dynamics by dedicator of cytokinesis 2 (DOCK2), a hematopoietic cell-specific actin effector protein, has been implicated in TCR signaling and T cell migration. Biallelic mutations in have been identified in patients with a recessive form of combined immunodeficiency with defects in T, B, and NK cell activation. Surprisingly, we show in this study that certain immune functions of CD8 T cells are enhanced in the absence of DOCK2. -deficient mice have a pronounced expansion of their memory T cell compartment. Bone marrow chimera and adoptive transfer studies indicate that these memory T cells develop in a cell-intrinsic manner following thymic egress. Transcriptional profiling, TCR repertoire analyses, and cell surface marker expression indicate that -deficient naive CD8 T cells directly convert into virtual memory cells without clonal effector T cell expansion. This direct conversion to memory is associated with a selective increase in TCR sensitivity to self-peptide MHC in vivo and an enhanced response to weak agonist peptides ex vivo. In contrast, the response to strong agonist peptides remains unaltered in -deficient T cells. Collectively, these findings suggest that the regulation of the actin dynamics by DOCK2 enhances the threshold for entry into the virtual memory compartment by negatively regulating tonic TCR triggering in response to weak agonists.
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http://dx.doi.org/10.4049/jimmunol.1900440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6920543PMC
January 2020

Luring T cells into a gray area.

Sci Immunol 2019 04;4(34)

Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Department of Medicine, Harvard University, Cambridge, MA 02139, USA. King Fahd Specialist Hospital-Dammam, Al Muraikabat, Dammam, Saudi Arabia. Email:

T cells that target β-synuclein induce damage to the gray matter of the brain in multiple sclerosis and contribute to neurodegeneration.
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http://dx.doi.org/10.1126/sciimmunol.aax3917DOI Listing
April 2019

Alterations in sialic-acid O-acetylation glycoforms during murine erythrocyte development.

Glycobiology 2019 03;29(3):222-228

Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.

We used Casd1-deficient mice to confirm that this enzyme is responsible for 9-O-acetylation of sialic acids in vivo. We observed a complete loss of 9-O-acetylation of sialic acid on the surface of myeloid, erythroid and CD4+ T cells in Casd1-deficient mice. Although 9-O-acetylation of sialic acids on multiple hematopoietic lineages was lost, there were no obvious defects in hematopoiesis. Interestingly, erythrocytes from Casd1-deficient mice also lost reactivity to TER-119, a rat monoclonal antibody that is widely used to mark the murine erythroid lineage. The sialic acid glyco-epitope recognized by TER-119 on erythrocytes was sensitive to the sialic acid O-acetyl esterase activity of the hemagglutinin-esterase from bovine coronavirus but not to the corresponding enzyme from the influenza C virus. During erythrocyte development, TER-119+ Ery-A and Ery-B cells could be stained by catalytically inactive bovine coronavirus hemagglutinin-esterase but not by the inactive influenza C hemagglutinin-esterase, while TER-119+ Ery-C cells and mature erythrocytes were recognized by both virolectins. Although the structure of the sialoglycoconjugate recognized by TER-119 was not chemically demonstrated, its selective binding to virolectins suggests that it may be comprised of a 7,9-di-O-acetyl form of sialic acid. As erythrocytes mature, the surfaces of Ery-C cells and mature erythrocytes also acquire an additional distinct CASD1-dependent 9-O-acetyl sialic acid moiety that can be recognized by virolectins from both influenza C and bovine coronavirus.
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http://dx.doi.org/10.1093/glycob/cwy110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381321PMC
March 2019

The Mst1 Kinase Is Required for Follicular B Cell Homing and B-1 B Cell Development.

Front Immunol 2018 17;9:2393. Epub 2018 Oct 17.

Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States.

The Mst1 and 2 cytosolic serine/threonine protein kinases are the mammalian orthologs of the Drosophila Hippo protein. Mst1 has been shown previously to participate in T-cell and B-cell trafficking and the migration of lymphocytes into secondary lymphoid organs in a cell intrinsic manner. We show here that the absence of Mst1 alone only modestly impacts B cell homing to lymph nodes. The absence of both Mst1 and 2 in hematopoietic cells results in relatively normal B cell development in the bone marrow and does not impact migration of immature B cells to the spleen. However, follicular B cells lacking both Mst1 and Mst2 mature in the splenic white pulp but are unable to recirculate to lymph nodes or to the bone marrow. These cells also cannot traffic efficiently to the splenic red pulp. The inability of late transitional and follicular B cells lacking Mst 1 and 2 to migrate to the red pulp explains their failure to differentiate into marginal zone B cell precursors and marginal zone B cells. Mst1 and Mst2 are therefore required for follicular B cells to acquire the ability to recirculate and also to migrate to the splenic red pulp in order to generate marginal zone B cells. In addition B-1 a B cell development is defective in the absence of Mst1.
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http://dx.doi.org/10.3389/fimmu.2018.02393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199389PMC
October 2019

JAKing up resistance to immunotherapy.

Sci Immunol 2017 10;2(16)

Ragon Institute of MGH, MIT and Harvard Department of Medicine, Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA. Email:

A two-cell type CRISPR screen has identified genes and pathways that mediate resistance to cancer immunotherapy.
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http://dx.doi.org/10.1126/sciimmunol.aaq0015DOI Listing
October 2017
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