The purpose of Th17 cells is to clear pathogens, which are not efficiently handled by TH1 and TH2 type of immunity. The induction of Th17 responses must go through three distinct steps: Induction, amplification and stabilization. The stability of Th17 population is only relevant if it is protective against a given pathogen-invader or other kind of insult. If Th17 cells loose their stability they become highly proinflammatory and promote the destruction of your body’s tissues as occurs in autoimmune conditions. In essence, your immune system chooses to sacrifice body tissues by destroying in order to preserve the rest of your body.
By promoting inflammation and attracting neutrophils, TH17-cells may help to remove microbes from the body. However, by triggering an excessive inflammatory response, TH17-cells can contribute to such inflammatory diseases as Hashimoto’s Thyroiditis, Crohn’s disease, Ulcerative Colitis, Psoriasis and many other Autoimmune conditions.
TH17 cells have recently emerged as a third independent type T cells which may play an essential role in protection against certain disease causing microbes. IL-17 plays an important and unique role protection against specific pathogens. The production of IL-17 and the recruitment of neutrophils is important in protection against gram-negative bacteria and fungal infections. Th17 are highly pro-inflammatory and that Th17 cells with specificity for self-antigens lead to severe autoimmunity.
Forbidden Cytokines and Autoimmunity
T-cells secrete various cytokines through which they affect a broad spectrum of normal and pathological immune processes. Cytokine secretion by helper T cells is particularly important in autoimmunity[i] because chronic autoimmune diseases, such as Hashimoto’s Thyroiditis, Multiple Sclerosis, Type 1 Diabetes, and Rheumatoid Arthritis are predominantly caused by Th1 cells. Th2 cells can antagonize Th1 functions[ii] and in numerous autoimmune conditions prevent and/or cure autoimmune diseases.
However, recent studies found exceptions to this rule, suggesting that the behavior of a given T cell population may be unpredictable in its cytokine secretion profile. For example, (i) Th2-type T cells can be not only inefficient suppressors of autoimmune conditions induced by Th1 cells,[iii] but can cause Autoimmune conditions;[iv] thus Th1 and Th2 cells can both promote autoimmune conditions; (ii) Th0-type T cells (producing both Th1 and Th2 cytokines) can stimulate autoimmune conditions and are able to instigate Autoimmune conditions;[v] and (iii) Th2-type T cells can induce pancreatitis and diabetes in immune-compromised nonobese individuals with blood sugar problems.[vi]
The cytokine secretion of the same T cell population is different in the lymph nodes (producing both Th1 and Th2 cytokines) than in the central nervous system (CNS) environment (producing only Th1 cytokines). This observation suggests that within the CNS, specific factors (mainly IL-12 producing microglia acting as APCs, not neurons) can modulate the cytokine secretion of Tcells, can select Th1/Th2 pathway, and can control effector CD4+ T cell cytokine profile in Autoimmune conditions.[vii]
Four neuropeptides (NPs): somatostatin, calcitonin gene-related peptide, neuropeptide Y, and substance P, in the absence of any additional factors, directly induce a increased secretion of cytokines [interleukin 2 (IL-2), interferon-g, IL-4, and IL-10) from T cells. Furthermore, these NPs drive distinct Th1 and Th2 populations to a ‘‘FORBIDDEN’’ cytokine secretion[viii]: secretion of Th2 cytokines from a Th1 T cell line and vice versa. Such a phenomenon cannot be induced by classical antigenic stimulation.
The nervous system, through these NPs interacting with their specific T cell-expressed receptors, can lead to the secretion of both typical and atypical cytokines, leading to the breakdown of the commitment to a distinct Th phenotype, and a potentially altered function and destiny of T cells in vivo.
Nerve fibers that release NPs are widespread in the mammalian central and peripheral nervous systems, in certain endocrine tissues, and in all the primary and secondary lymphoid organs.[ix]
Yeast/Fungi (ingested mold in this case) synthesize somatostatin using it as a defense mechanism to create their ideal environment. Normally, somatostatin is produce by the body in the gastrointestinal tract, pancreas and regions of the CNS. Classified as an inhibitory hormone, it has been shown to impede proinflammatory responses. Somatostatin secreted from non-neuronal cells along the digestive tract plays an important role as a mediator during mucosal inflammatory responses after physiological (induced by TNF-α) and pathophysiological (up-regulation of bacteria) stimulations. TH1, which predominates gastritis (gut inflammation), may be quelled through the increased levels of somatostatin. Through reduced inflammation, the yeast and other microbes are able to avoid attack by the TH1 immune system.
Yeast (Saccharomyces cerevisiae) used in probiotics, synthesizes an analogous peptide hormone precursor, pro a-factor, which is proteolytically processed by at least two separate proteases, the products of the KEXZ and STE13 genes, to generate the mature bioactive peptide somatostatin (SMS).[i],[ii],[iii],[iv],[v]
Expression in yeast of recombinant DNAs encoding hybrids between the proregion of a-factor and somatostatin results in proteolytic processing of the chimeric precursors and secretion of mature somatostatin.[vi]