*MS4A1, CD79A, CD79B positive CD8+ T cells.
Experimental studies show that enhanced TGF-β signalling and HIF expression contribute to the progression of tumors [165]. HIF signalling contributes to the etiopathology of various autoimmune diseases, including multiple sclerosis (MS) [166]. MS and other severe neurological disorders, including Alzheimer’s, can emerge as causalities of the anti-SARS-CoV-2 mRNA vaccination and spike protein side effects [167,168]. Moreover, the combination of a) IL-6 and TNF-α overexpression, b) enhanced TGF-β signalling and c) increase of HIF expression by the anti-SARS-CoV-2 vaccine spike protein can be detrimental for the development of the Treg response and lead directly to autoimmunity [169].
As illustrated in Figure 3, HIF overexpression increases TGF-β signalling [170]. At the same time, the abundance of IL-6, when accompanied by the overexpression of TNF-α, results in the decrease of CD4+, CD25+(high), Foxp3+ Treg cells, and the increase of IL-17-producing T helper (Th17) cells [171]. In addition, the expression of TGF-β, in tandem with IL-6, represses Foxp3 expression and enhances CD17 expression and hence growth of a Th17 cell subpopulation via RORγt nuclear receptor expression and activation of signal transducer and activator of transcription 3 (STAT3) [172,173]. The spike protein has been shown to activate both TLR2 and TLR4, resulting in JAK/STAT signalling [174-176].