Cross-regulation between the nervous system and type 2 immunity

This paper just popped up on X.

Might be a useful summary.

Cross-regulation between the nervous system and type 2 immunity

https://www.science.org/doi/10.1126/sciimmunol.adp6450


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Abstract

Interactions between the nervous and immune systems are critical to healthy physiology and are altered in many human diseases. Many of the major players in type 2 immune responses, including type 2 lymphocytes and cytokines, mast cells, and immunoglobulin E, have been implicated in neuronal function and behavior. Conversely, neurons in both the central and peripheral nervous systems can affect type 2 immune responses and behaviors relevant to allergy, such as food avoidance. Defining this complex circuitry and its molecular intermediates in physiology may reveal type 2 immunomodulators that can be harnessed for therapeutic benefit in neurologic diseases including Alzheimer’s disease, brain injury, and neurodevelopmental disorders. Conversely, modulation of the nervous system may be an important adjunct to treating immunologic disorders including atopic dermatitis, asthma, and food allergy. This Review covers recent work defining how the nervous system can both regulate and be regulated by type 2 immune responses.

Nicholas M. Mroz et al. ,

Cross-regulation between the nervous system and type 2 immunity.Sci. Immunol.10,eadp6450(2025).DOI:10.1126/sciimmunol.adp6450

 

I thin they must mean type 2 innate lymphoid cells. I have never heard of type 2 lymphocytes and nor has Google's AI service! Judging by the abstract it seems to focus on allergy so probably isn't of much relevance to ME/CFS.

 

I assumed it would include Th2 cells?

 

It seems that there are other cells that produce similar cytokines to 'TH2' cells that are involved in IgE production and parasite immunity.

I have not heard of the idea of 'type 2 immune response'. In Coombs and Gell terms IgE responses are type I hypersensitivity, not type II. A TH2 response is basically an antibody response and not what they are talking about here. Maybe this is standard terminology for parasitologists but it seems odd to me.

 

Judging by the first reference, by one of the authors (Molofsky), it looks like you are both right.

https://pmc.ncbi.nlm.nih.gov/articles/PMC10120575/

I feel allergy is relevant to the kind of ME I have aka CFIDS because my experience at onset of recurring HSV2 virus, post EBV, was accompanied by a novel and very severe allergic asthmatic and eczematic reaction to grass pollen, diagnosed by the late Prof J Brostoff using a skin prick panel test, who unfortunately did not know enough to diagnose ME or anything else but did share useful tips on avoiding stimulating amines in my diet to help with the cognitive difficulties which accompanied all of this, along with the paradoxical and contrasting zombie like state of low energy etc.

TH2 shift featured in Dr Paul Cheney's hypotheses, which I read after I was first diagnosed with ME/CFS in 1996 and felt this corroborated and was corroborated by my experience of onset of chronically active recurring virus accompanied by novel pronounced allergy. I appreciate not everyone with ME experiences viral onset or recurring virus or increased allergic responses but I take comfort that enough do that Dr Cheney developed an hypothesis to account for it.

Perhaps ME/CFIDS should be considered a subtype of ME/CFS? At any rate I feel the clinical observations which lead to the TH2 shift hypothesis need to be understood better for scientific and clinical purposes even if one does not agree with the hypothesis or nomenclature.

 

To be honest I think the 'TH2 shift', as for the 'TH1 shift' idea, should be dead and buried by now. It never made any sense and never yielded any useful models.

It looks to me as if maybe one of the authors of this paper has invented his own 'Type 2 Immunity' idea. Which should probably be buried alongside its insubstantial friends in the cemetery of dud ideas.

 

I think it was Janeway's Immunobiology I remember it from, though I don't have access to it now, that said
type 1 response is mainly ILC1, Th1, and IgG for intracellular pathogens,
type 2 is ILC2, Th2, and IgE for parasites/intestinal bacteria,
and type 3 is ILC3, Th17, and maybe IgA for extracellular bacteria/fungi, not sure about IgA in the last one.

 

That would figure. Charlie Janeway and Polly with the yellow boots in the 1990s. I always saw that sort of pigeonholing as unhelpful. Every response involves the whole system in varying degrees.

Attempts to apply this sort of model to rheumatic disease held us up for a decade. The have held up understanding of MS for three decades.