Natural killer cells in human autoimmune diseases

[heapsreal]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2999796/
Conclusion

While inappropriate activation of cells of the adaptative immune response was mainly reported in autoimmune diseases, numerous observations suggest a role for NK cells in these disorders. To date, NK cells have not been specifically targeted by treatments of autoimmune diseases. However, some biotherapies are associated with changes in the circulating NK compartment. For example, daclizumab (anti-IL-2Rα) in multiple sclerosis is associated with an increase in the number of CD56bright NK cells.56 The same change is observed in the treatment of uveitis with daclizumab.57 Interestingly, the expansion of blood NK cells has been found to be correlated with the suppression of disease activity, and NK cells isolated from patients during treatment were able to kill autologous-activated T cells.56 From another point of view, NK cells play an important role, through ADCC, in the efficacy of monoclonal antibodies used to treat human diseases.38 Thus, identifying the modifications of NK cells and the role of NK cells in autoimmune diseases will help to define new therapeutic targets and to optimize the efficiency of current biotherapies in such indications.

It has been suggested that NK cells have a disease-promoting or a disease-controlling role in autoimmune diseases, depending on the disease and the NK cell subset analysed. A disease-controlling role is clearly suggested by studies in SLE patients in which circulating NK cells are reduced in number and functions. These abnormalities have been shown to correlate with some clinical manifestations of the disease. Such modifications of NK cells mirror the protective role of NK cells proposed in the model of multiple sclerosis where an increase in the numbers of circulating NK cells correlates with remission of the disease. However, despite clinical correlative evidence, the mechanisms by which NK cells control autoimmune disease remain unknown. Moreover, it is difficult to reconcile the dual NK cell roles in different autoimmune diseases. Perhaps NK cells can have either a protective or a disease-promoting role in a given autoimmune disease at different stages of the disease (e.g. onset and/or progression) in a several-year-long process. Thus, forthcoming studies should focus on tissue NK cells and NK cell interactions with other immune cells at sites of inflammation at different phases of the development of autoimmune diseases.

 

[Enid]

Interesting heaps - my brother worse affected is tipped into autoimmune (liver) though viral damage (CNS) has been diagnosed. I can think of some genetic weakness - but much more of collapse of the immune system - due to a persisting viral infection - mine revealing weak anti-smooth muscle antibodies - EBV et al. not diagnosed.

 

[heapsreal]

hi enid,

its interesting how its mentions autoimmune illness or persistent viral infection. So theres another 2 possible subgroups. those with an autoimmune illness are also prone to viral infections and i think could look alot like those with just persistent viral infections, maybe that could be a difference between responders and non responders with antivirals??

it would be nice if there were more treatments for nk dysfunction. treatment for those born with very low nk cells, not neccessarily function, are mostly just placed on antivirals to stop viral replication, immunoglobulins are used. Nothing really out of the box we dont already know.

In a perfect world there would be something that would definately increase nk function, bright and dim nk function and then see if people improve?? or is it just a marker of persistent viral infections and autoimmune illnesses??
http://www.uptodate.com/contents/nk-cell-deficiency-syndromes-treatment

 

[heapsreal]

another short study review http://www.ncbi.nlm.nih.gov/pubmed/12505527
Abstract

There are a surprisingly large number of human natural killer (NK) cell deficiency states that provide insight into the role of NK cells in defense against human infectious disease. Many disorders associated with NK cell defects are caused by single gene mutations and, thus, give additional understanding concerning the function of specific molecules in NK cell development and activities. A resounding theme of NK cell deficiencies is susceptibility to herpesviruses, suggesting that unexplained severe herpesviral infection should raise the possibility of an NK cell deficit.

 

[Husband of]

Not sure if you’ve seen this one heapsreal. I don’t have Elsevier access and would t really understand the article if I did, but it sounds interesing

https://pubmed.ncbi.nlm.nih.gov/30122459/

Abstract

First described 40 years ago, natural killer (NK) cells represent the founding members of the innate lymphoid cell (ILC) family. They were initially defined by their ability to kill cancer cells of hematopoietic origin. More recently, NK cells are recognized not only for their ability to kill infected or malignant cells, but also for mediating cytotoxicity against a range of normal immune cells. They thereby play an important physiological role in controlling immune responses and maintaining homeostasis. Besides cytotoxic activity, NK cells activation is accompanied by secretion of pro-inflammatory cytokines. Hence, NK cells have the potential to act both in driving inflammation and in restricting adaptive immune responses that may otherwise lead to excessive inflammation or even autoimmunity. Here, we highlight how NK cell activity is linked to inflammasome activation and review new molecular insights to the roles of NK cells in inflammation and autoimmunity. Furthermore, in light of new insights to NK cell differentiation and memory, we deliberate on how distinct NK cell subsets may impact immunoregulatory functions. Hypothetically, memory-like or adaptive NK cells could drive NK cell-mediated autoreactive diseases. Together, new findings underscore the complex yet important physiological roles of NK cells in both promoting inflammation and exerting immunoregulation and maintenance of immune homeostasis. Insights raise intriguing questions as to how NK cells themselves maintain self-tolerance.

 

[heapsreal]

Not sure if you’ve seen this one heapsreal. I don’t have Elsevier access and would t really understand the article if I did, but it sounds interesing

https://pubmed.ncbi.nlm.nih.gov/30122459/

Abstract

First described 40 years ago, natural killer (NK) cells represent the founding members of the innate lymphoid cell (ILC) family. They were initially defined by their ability to kill cancer cells of hematopoietic origin. More recently, NK cells are recognized not only for their ability to kill infected or malignant cells, but also for mediating cytotoxicity against a range of normal immune cells. They thereby play an important physiological role in controlling immune responses and maintaining homeostasis. Besides cytotoxic activity, NK cells activation is accompanied by secretion of pro-inflammatory cytokines. Hence, NK cells have the potential to act both in driving inflammation and in restricting adaptive immune responses that may otherwise lead to excessive inflammation or even autoimmunity. Here, we highlight how NK cell activity is linked to inflammasome activation and review new molecular insights to the roles of NK cells in inflammation and autoimmunity. Furthermore, in light of new insights to NK cell differentiation and memory, we deliberate on how distinct NK cell subsets may impact immunoregulatory functions. Hypothetically, memory-like or adaptive NK cells could drive NK cell-mediated autoreactive diseases. Together, new findings underscore the complex yet important physiological roles of NK cells in both promoting inflammation and exerting immunoregulation and maintenance of immune homeostasis. Insights raise intriguing questions as to how NK cells themselves maintain self-tolerance.

I can't say I fully understand it either . But I feel frustrated that the low nk function in cfsme just hasn't been pursued enough as well as good treatments to improve nk function. It's an abnormality commonly found in us, yet I don't think enough has been done about it. The carry over to treating other conditions I think will be broad, from MS and autoimmune issues to treating cancers.

Ampligen was a drug that improved nk function and symptoms in cfsme but I think if they pursued this treatment they would have improved it alot in 30yrs.
Frustrating

 

[Learner1]

But I feel frustrated that the low nk function in cfsme just hasn't been pursued enough as well as good treatments to improve nk function. It's an abnormality commonly found in us, yet I don't think enough has been done about it. The carry over to treating other conditions I think will be broad, from MS and autoimmune issues to treating cancers

I agree. It is common. As a stage 3 cancer survivor, I've learned that many modern treatments that can be used to fight cancers rely on NK cell function to work, leaving those of us with low NK cell function vulnerable.

It's not just NK cells - I had a test done last year where they put my killer T cells (cytotoxic T lymphocytes) at different strengths in petri dishes with cancer cells and my cells didn't kill the cancer cells. I've discussed this with two cancer centers and two immunologists and nobody, except my naturopathic doctor, seems very interested, yet this is my biggest fear. I know that cancer is not unheard of in other ME/ CFS patients.

My immunologist's explanation was that I have T call exhaustion, but he didn't know what to do with it.

 

[Pyrrhus]

I had a test done last year where they put my killer T cells (cytotoxic T lymphocytes) at different strengths in petri dishes with cancer cells and my cells didn't kill the cancer cells. I've discussed this with two cancer centers and two immunologists and nobody, except my naturopathic doctor, seems very interested, yet this is my biggest fear.

Did anyone discuss if you would be a candidate for CAR-T therapy?

 

[heapsreal]

I agree. It is common. As a stage 3 cancer survivor, I've learned that many modern treatments that can be used to fight cancers rely on NK cell function to work, leaving those of us with low NK cell function vulnerable.

It's not just NK cells - I had a test done last year where they put my killer T cells (cytotoxic T lymphocytes) at different strengths in petri dishes with cancer cells and my cells didn't kill the cancer cells. I've discussed this with two cancer centers and two immunologists and nobody, except my naturopathic doctor, seems very interested, yet this is my biggest fear. I know that cancer is not unheard of in other ME/ CFS patients.

My immunologist's explanation was that I have T call exhaustion, but he didn't know what to do with it.

Griffith university in Australia, one of the few places digging deep onto nk research, have also shown that T cell function is low like nk cells in cfsers. If I recall correctly it was cd8 T cells.
Dr Peterson I think has mentioned that he has he seen a higher than normal amount of rare cancers in cfsme.
T cell exhaustion, maybe the T cells have cfsme , if only those T cells could have a positive attitude??? If I don't laugh I'd cry.

 

[godlovesatrier]

The long covid t and NK cell research is shining s bit of a light on this area.

Dr Leonardi has already proven naive t cells exist and if you loose some of those that's it you're never getting them back.
That aside I think the t and NK cells are also really quite complex maybe more than we first understood. So yes there could be secondary reasons why they might not take out cancer cells properly for example.

It's a really interesting area lots of new science about. Sadly a lot of it gets buried with mainstream media articles that are utter garbage. As for the t cell exhaustion that's one hundred percent a thing. Which is why I mentioned naive t cells. I am not even sure if we have a test that can be used to figure out how many naive t cells a person has. Or what the borometer would be for "no longer having a healthy level." But I find it all really fascinating and scary.

 

[Violeta]

I didn't know olive leaf improves natural killer cell count.

I have some but don't take it regularly because it can also lower blood pressure. I am going to take licorice root along with it and see if I can tolerate it better.

The results showed higher values of CD3-/CD16/56 (NK) cells, CD3+/CD16/56 (NKT) cells, total NK (NK+NKT) cells, and serum IFN-gamma and IL-2 levels in OLT drinkers as compared to the nondrinkers.

https://clinicaltrials.gov/ct2/show/NCT05222347

 

[Violeta]

Panax ginseng (P. ginseng) root is a complementary and alternative medicine (CAM) typically used in traditional Asian medicine. We have reported that oral consumption of the P. ginseng aqueous extract (PgE) by mice augments natural killer (NK) cell activity, which is critical for immune surveillance against tumors.

Effect of oral consumption of Panax ginseng aqueous extract on natural killer cell cytotoxicity in humans

https://www.sciencedirect.com/scien...ng (P.,for immune surveillance against tumors.