scholarly journals The Perfect Storm Review: Immune Dysregulation in Severe COVID-19 and the Possible Role of Mast Cell-Vitamin D Interactions

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Houldsworth A
Keyword(s):  
Vitamin D ◽  
Mast Cell ◽  
Cell Differentiation ◽  
T Cell ◽  
Immune Responses ◽  
Cell Activation ◽  
T Cell Differentiation ◽  
Innate Immune ◽  
Host Cells ◽  
Mast Cell Activation

COVID-19 is caused by a Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) and has two spike subunits on the envelope of SARS-CoV-2, S1 and S2, where S1 binds to the Angiotensin Converting Enzyme (ACE-2), a receptor on the host cells and S2 binds to the cell surface membrane. Different immune responses to the virus are apparent, from asymptomatic to severe respiratory distress, organ failure and ultimately death. Immune responses without hyper-inflammation are essential to successful viral resolution. Pathological and environmental factors drive the immunological repertoire, in response to the virus, influencing innate immune cell activation, cytokine-balance and T cell differentiation. This is determined by age, comorbidity, Vitamin D status and ethnicity related factors. Homeostasis of the immune system plays an important role in the development of COVID-19 pneumonia. Mast cell activation and release of histamine is important to the cytokine driven T-cell differentiation as the adaptive response. This review combines the relative effects of UV-index-related Vitamin-D synthesis with immune status. Innate immune responses, T cell differentiation and renin/angiotensin system are different in patients affected by COVID-19 and their different outcomes are explored.

scholarly journals The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation

2016 ◽  
Vol 171 (3-4) ◽  
pp. 203-208 ◽  
Author(s):  
Pazit Salamon ◽  
Irit Shefler ◽  
Alon Y. Hershko ◽  
Yoseph A. Mekori
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Protein Kinase ◽  
Cell Activation ◽  
Mast Cell Activation ◽  
Protein Kinase D

scholarly journals MicroRNA-4443 regulates mast cell activation by T cell–derived microvesicles

2018 ◽  
Vol 141 (6) ◽  
pp. 2132-2141.e4 ◽  
Author(s):  
Irit Shefler ◽  
Pazit Salamon ◽  
Francesca Levi-Schaffer ◽  
Adam Mor ◽  
Alon Y. Hershko ◽  
...  
Keyword(s):  
Mast Cell ◽  
T Cell ◽  
Cell Activation ◽  
Mast Cell Activation

scholarly journals HIV-TB coinfection impairs CD8+T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

2015 ◽  
Vol 45 (9) ◽  
pp. 2529-2541 ◽  
Author(s):  
Guadalupe V. Suarez ◽  
Matías T. Angerami ◽  
María B. Vecchione ◽  
Natalia Laufer ◽  
Gabriela Turk ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
And Function

Generation and biochemical analysis of human effector CD4 T cells: alterations in tyrosine phosphorylation and loss of CD3ζ expression

Blood ◽  
2001 ◽  
Vol 97 (12) ◽  
pp. 3851-3859 ◽  
Author(s):  
Sandeep Krishnan ◽  
Vishal G. Warke ◽  
Madhusoodana P. Nambiar ◽  
Henry K. Wong ◽  
George C. Tsokos ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Tyrosine Phosphorylation ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Effector T Cells ◽  
T Cell Differentiation ◽  
Effector T Cell

Human effector T cells have been difficult to isolate and characterize due to their phenotypic and functional similarity to the memory subset. In this study, a biochemical approach was used to analyze human effector CD4 T cells generated in vitro by activation with anti-CD3 and autologous monocytes for 3 to 5 days. The resultant effector cells expressed the appropriate activation/differentiation markers and secreted high levels of interferon γ (IFN-γ) when restimulated. Biochemically, effector CD4 T cells exhibited increases in total intracellular tyrosine phosphorylation and effector-associated phosphorylated species. Paradoxically, these alterations in tyrosine phosphorylation were concomitant with greatly reduced expression of CD3ζ and CD3ε signaling subunits coincident with a reduction in surface T-cell receptor (TCR) expression. Because loss of CD3ζ has also been detected in T cells isolated ex vivo from individuals with cancer, chronic viral infection, and autoimmune diseases, the requirements and kinetics of CD3ζ down-regulation were examined. The loss of CD3ζ expression persisted throughout the course of effector T-cell differentiation, was reversible on removal from the activating stimulus, and was modulated by activation conditions. These biochemical changes occurred in effector T cells generated from naive or memory CD4 T-cell precursors and distinguished effector from memory T cells. The results suggest that human effector T-cell differentiation is accompanied by alterations in the TCR signal transduction and that loss of CD3ζ expression may be a feature of chronic T-cell activation and effector generation in vivo.

scholarly journals Granzyme B skews CD4+ T cell differentiation resulting in increased intestinal pathogenicity

2020 ◽  
Author(s):  
Kristen L. Hoek ◽  
Michael J. Greer ◽  
Kathleen G. McClanahan ◽  
Ali Nazmi ◽  
M. Blanca Piazuelo ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
Immune Responses ◽  
Cell Biology ◽  
Intestinal Inflammation ◽  
Granzyme B ◽  
Disease Onset ◽  
T Cell Differentiation ◽  
Transfer Model

AbstractCD4+ T cell activation and differentiation are important events that set the stage for proper immune responses. Many factors are involved in the activation and differentiation of T cells, and these events are tightly controlled to prevent unwanted and/or exacerbated immune responses that may harm the host. It has been well documented that granzyme B, a potent serine protease involved in cell-mediated cytotoxicity, is readily expressed by certain CD4+ T cells, such as regulatory T cells and CD4+CD8aa+ intestinal intraepithelial lymphocytes, both of which display cytotoxicity associated with granzyme B. However, because not all CD4+ T cells expressing granzyme B are cytotoxic, additional roles for this protease in CD4+ T cell biology remain unknown. Here, using a combination of in vivo and in vitro approaches, we report that granzyme B-deficient CD4+ T cells display increased IL-17 production. In the adoptive transfer model of intestinal inflammation, granzyme B-deficient CD4+ T cells triggered a more rapid disease onset than their WT counterparts, and presented a differential transcription profile. Similar results were also observed in granzyme B-deficient mice infected with Citrobacter rodentium. Our results suggest that granzyme B modulates CD4+ T cell differentiation, providing a new perspective into the biology of this enzyme.

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