Th17, newly discovered immunity plays a pivotal role in Acne/Isotretinoin

Im sure some of you have heard of th1 and th2 cell type immunity.
Th17 immunity was discovered in 2005, over 20 years after the release of Accutane.
Retinoids could target th17 immunity, with possible consequence.
This might be something to look into.

Propionibacterium acnes and the Th1/Th17 Axis, Implications in Acne Pathogenesis and Treatment

2017


Acne vulgaris is one of the most commonly seen conditions and the immunological link is a topic of active research. Recently, the Th17 pathway has been found to play a pivotal role in acne. The adaptive immune response toward Propionibacterium acnes leads to activation of Th17 axis. Consequently, the Th17 cytokines (IL-17, IL-1 β, IL-6, and tumor growth factor, in turn, activate the various pathogenic steps in acne. Drugs such as Vitamin D3 and isotretinoin which target the Th17 pathway may offer an additional pathway for their therapeutic response.

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Th17 cells in human disease

Our understanding of the role of T cells in human disease is undergoing revision as a result of the discovery of T-helper 17 (Th17) cells, a unique CD4+ T-cell subset characterized by production of interleukin-17 (IL-17). IL-17 is a highly inflammatory cytokine with robust effects on stromal cells in many tissues. Recent data in humans and mice suggest that Th17 cells play an important role in the pathogenesis of a diverse group of immune-mediated diseases, including psoriasis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and asthma. Initial reports also propose a role for Th17 cells in tumorigenesis and transplant rejection. Important differences, as well as many similarities, are emerging when the biology of Th17 cells in the mouse is compared with corresponding phenomena in humans. As our understanding of human Th17 biology grows, the mechanisms underlying many diseases are becoming more apparent, resulting in a new appreciation for both previously known and more recently discovered cytokines, chemokines, and feedback mechanisms. Given the strong association between excessive Th17 activity and human disease, new therapeutic approaches targeting Th17 cells are highly promising, but the potential safety of such treatments may be limited by the role of these cells in normal host defenses against infection.

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Couple more studies and thoughts I wanted to pin to this.
I like how it describes war vs peace and when its appropriate.

The Effect of Probiotics and Gut Microbiota on Th17 Cells

Probiotics and gut microbiota have a significant impact on gut homeostasis in the host. Recent clinical studies demonstrated the ameliorative features of several kinds of probiotics in intestinal disorders, such as inflammatory bowel diseases (IBDs). Interleukin (IL)-17 is a potent inflammatory cytokine, and T-helper (Th)17 cells and other IL-17-producing cells are involved in the pathogenesis of IBD. Multiple mechanisms of action have been suggested to explain the protective anti-inflammatory effects of probiotics in intestinal inflammation, including the immunoregulation and suppression of Th17 activity and IL-17 production in part by signaling through pattern-recognition receptors such as Toll-like receptor family. However, steady-state Th17 cells have an important role in host defense against fungi and bacteria. Interestingly, recent studies revealed that specific commensal bacterial species such as segmented filamentous bacteria (SFB) induce the accumulation of Th17 cells in the small intestine in many species, including mice. It is important to determine the mechanisms by which intestinal Th17 cells are induced by SFB and whether these or other bacteria with similar properties are present in the human intestine. This brief review focuses on the interaction between probiotics/microbiota and Th17 cells during inflammation (war) and during steady-state homeostatic regulation (peace).

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Are Th17 cells in the gut pathogenic or protective?

https://www.nature.com/articles/mi201151

A quick example of how far this can go,
**The gut – eye axis: can our intestines influence our eye health?
**www.college-optometrists.org › the-college › blogs › can-our-intestin…
by M Bowen - ‎2019 - ‎Related articles
May 28, 2019 - But the emerging evidence points to far more complex links between the health of our guts and that of our eyes. What we eat may affect our eye …

Bacteria in Gut Could Be Cause of Disease in the Eye

www.healthline.com › health-news › bacteria-in-gut-could-be-cause-o…
](https://www.healthline.com/health-news/bacteria-in-gut-could-be-cause-of-disease-in-the-eye-081815)

Aug 18, 2015 - Researchers theorize that a certain type of gut bacteria triggers T cells to invade the eye . Now, they’re focusing on how to prevent that from …

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More notes.

Microbial-Induced Th17: Superhero or Supervillain?

Th17 cells are an effector lineage of CD4 T cells that can contribute to protection against microbial pathogens and to the development of harmful autoimmune and inflammatory conditions. An increasing number of studies suggests that Th17 cells play an important protective role in mobilizing host immunity to extracellular and intracellular microbial pathogens, such as Candida and Salmonella . Furthermore, the generation of Th17 cells is heavily influenced by the normal microbial flora, highlighting the complex interplay among harmless microbes, pathogens, and host immunity in the regulation of pathogen-specific Th17 responses. In this article, we review the current understanding of microbe-induced Th17 cells in the context of infectious and inflammatory disease.

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Updating this. If this was a possibility with Accutane,

Th17 cells play an important role in maintaining mucosal barriers and contributing to pathogen clearance at mucosal surfaces; such protective and non-pathogenic Th17 cells have been called Treg17 cells .[2]

They have also been implicated in autoimmune and inflammatory disorders. The loss of Th17 cell populations at mucosal surfaces has been linked to chronic inflammation and microbial translocation.

i’ve posted on this before,

Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan

and this,

The effects of systemic isotretinoin and antibiotic therapy on the microbial floras in patients with acne vulgaris.


The aim of this study was to investigate the effects of systemic isotretinoin and antibiotic therapy on the microbial floras of oropharynx, nose and feces in acne patients.

METHODS:

Treatment groups of isotretinoin and antibiotics consisting of 20 and 15 patients, respectively were included. Microbiological culture samples were taken at baseline and once a month during 4-6 months of treatment period.

RESULTS:

Difference in microbial flora throughout the treatment period was detected at least among one of all culture samples of 15 (75%) and 5 (33%) patients in isotretinoin and antibiotic groups. There was statistically significant difference between two groups in means of alteration of the microbial flora (P = 0.013). The difference was definitely observed among nasal cultures (65%) in isotretinoin group and fecal cultures (20%) in the other. Staphylococcus aureus colonization was prominent in the microbial floras of nose and oropharynx and 2 of 14 nasal isolates were detected to be methicilline resistant while Escherichia coli with extended spectrum beta lactamase activity was detected in fecal floras of patients in isotretinoin group.
Systemic isotretinoin and antibiotic treatments in acne patients precisely caused variations in the microbial floras of several sites of the body, while isotretinoin was commonly more responsible than antibiotics. Knowing that alterations in the microbial colonization of the flora regions may preceede infectious disease and bacterial resistance, treatment options and follow-up procedures in acne vulgaris should be carefully determined to reduce the risk of destruction of the microbial flora.

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Looking at this possible other pathway, you see how this can work.
So when people have setbacks or take longer to recover after taking (fill in the blank supplement)
There could be other factors at play as well as to why a person might find themselves in a deeper hole.

Zinc supplementation modulates T helper 17 cells via the gut microbiome

Zinc is a dietary micronutrient that regulates various biological processes. Zinc is important for replication and survival of microbes and, as a result, a common strategy of the immune system is to steal zinc away from disease-causing microbes to prevent their growth. Recent studies show that changes in levels of dietary zinc can alter the composition of the gut microbiota, however how this impacts mucosal immune responses in the gut is not known. Here, we show that supplementing mice with zinc sulphate, a commonly used therapy for treating diarrheal episodes, in drinking water for a week resulted in significant changes in gut microbial composition as well drastic reduction in microbial diversity. More importantly. we saw that zinc supplementation attenuated the T helper17 cell number and activity in murine small intestine. To determine if zinc-dependent changes in gut microbiota are sufficient to limit Th17 response, we transplanted the microbiome from zinc treated mice into germ-free mice. We saw that germ-free mice that received cecal contents from zinc treated mice have reduced Th17 response, thus establishing that dietary zinc changes immune potential of the gut microbiome. Th17 cells mediate antimicrobial response in the gut and are involved in the pathogenesis of many autoimmune diseases. Our work thus provides a novel nutritional approach for remodeling microbiota to dampen inflammatory immune responses in the gut.

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Looking at the potential of some other substances that have been mentioned on here, th17 immunity could also play a role in expulsion (clearance) and cold/flu symptoms.

The Role of Flavonoids in Inhibiting Th17 … - Hindawi

www.hindawi.com › journals › jir
](https://www.hindawi.com/journals/jir/2018/9324357/)

by D Kelepouri - ‎2018 - ‎Cited by 7 - ‎Related articles

Abstract. Flavonoids have been considered powerful anti-inflammatory agents, and their exact immunomodulatory action as therapeutic agents in autoimmune diseases has started to emerge. Their role in the manipulation of immunoregulation is less understood.

Role of Vitamin D[edit]

The active form of vitamin D (1,25-Dihydroxyvitamin D3) has been found to ‘severely impair’ [32] production of the IL-17 and IL-17F cytokines by Th17 cells.
Thus, active form of vitamin D is a direct inhibitor for Th17 differentiation.

Serotonin decreases the production of Th1/Th17 cytokines …

](https://onlinelibrary.wiley.com/doi/full/10.1002/eji.201847525)

by PM Sacramento - ‎2018 - ‎Cited by 9 - ‎Related articles

IL - 17 promotes viral infections and mediates viral infection -induced pathology. Despite its protective roles in the suppression of viral infections and infection -induced organ pathology, IL - 17 has also been strongly associated with promotion of viral infections and tissue pathology.Jul 24, 2019

TGFβ-activation by dendritic cells drives Th17 induction and intestinal contractility and augments the expulsion of the parasite Trichinella spiralis in mice

and no im not saying anyone has worms, its just an example.

A few more thoughts,

The Treg/Th17 Axis: A Dynamic Balance Regulated by the Gut Microbiome

T-helper 17 (Th17) and T-regulatory (Treg) cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect the host from pathogenic microorganisms and to restrain excessive effector T-cell responses

the fate of antigen-naïve T-cells to either Th17 or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6, and all-trans retinoic acid

Role of Short Chain Fatty Acids in Controlling Tregs and Immunopathology

SCFA Administration Partially Restores Protective Host Defense

Administration of SCFA Partially Restores Th17 and Treg Cells

By enhancing the Treg numbers and possibly functions, SCFA derived from resident bacteria play unequivocal role in promoting protective Th17 cells. Thus our results have identified previously unknown functions of SCFA in Th17 mediated anti-microbial resistance in oral mucosa. Excessive or reduced SCFA may be a sign of commensal dysbiosis and pre-disposition to pathogenic infections and inflammation in humans.

Mostly notes atm.

Just dropping some notes.

Downregulation of Th17 Cells in the Small Intestine by
Disruption of Gut Flora in the Absence of Retinoic Acid

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

https://www.pnas.org/content/113/50/E8141#sec-23