Editing Multiple sclerosis (section)

=== Other emerging theories ===
One emerging hypothesis, referred to as the hygiene hypothesis, suggests that early-life exposure to infectious agents helps to develop the immune system and reduces susceptibility to allergies and autoimmune disorders. The hygiene hypothesis has been linked with MS and [[microbiome]] hypotheses.<ref>{{cite journal | vauthors = Wasko NJ, Nichols F, Clark RB | title = Multiple sclerosis, the microbiome, TLR2, and the hygiene hypothesis | journal = Autoimmunity Reviews | volume = 19 | issue = 1 | pages = 102430 | date = January 2020 | pmid = 31734400 | doi = 10.1016/j.autrev.2019.102430 | doi-access = free }}</ref>

It has also been proposed that certain bacteria found in the gut use molecular mimicry to infiltrate the brain via the [[gut–brain axis]], initiating an inflammatory response and increasing blood-brain barrier permeability. [[Vitamin D]] levels have also been correlated with MS; lower levels of vitamin D correspond to an increased risk of MS, suggesting a reduced prevalence in the tropics – an area with more Vitamin D-rich sunlight – strengthening the impact of geographical location on MS development.<ref>{{cite journal | vauthors = Aranow C | title = Vitamin D and the immune system | journal = Journal of Investigative Medicine | volume = 59 | issue = 6 | pages = 881–886 | date = August 2011 | pmid = 21527855 | pmc = 3166406 | doi = 10.2310/jim.0b013e31821b8755 }}</ref> MS mechanisms begin when peripheral [[Autoreactive lymphocyte|autoreactive]] effector [[CD4+ T cells]] get activated and move into the CNS. [[Antigen-presenting cell]]s localize the reactivation of autoreactive effector CD4-T cells once they have entered the CNS, attracting more T cells and macrophages to form the inflammatory lesion.<ref>{{cite journal | vauthors = Tada T, Takemori T, Okumura K, Nonaka M, Tokuhisa T | title = Two distinct types of helper T cells involved in the secondary antibody response: independent and synergistic effects of Ia- and Ia+ helper T cells | journal = The Journal of Experimental Medicine | volume = 147 | issue = 2 | pages = 446–458 | date = February 1978 | pmid = 415110 | pmc = 2184496 | doi = 10.1084/jem.147.2.446 }}</ref> In MS patients, macrophages and microglia assemble at locations where demyelination and neurodegeneration are actively occurring, and microglial activation is more apparent in the normal-appearing white matter of MS patients.<ref>{{cite journal | vauthors = Lassmann H | title = Multiple Sclerosis Pathology | journal = Cold Spring Harbor Perspectives in Medicine | volume = 8 | issue = 3 | pages = a028936 | date = March 2018 | pmid = 29358320 | pmc = 5830904 | doi = 10.1101/cshperspect.a028936 }}</ref> [[Astrocyte]]s generate neurotoxic chemicals like [[nitric oxide]] and [[TNFα]], attract neurotoxic inflammatory [[monocyte]]s to the CNS, and are responsible for [[astrogliosis]], the scarring that prevents the spread of neuroinflammation and kills neurons inside the scarred area.<ref>{{cite book | vauthors = Minagar A, Shapshak P, Alexander JS | chapter = Pathogenesis of HIV-Associated Dementia and Multiple Sclerosis: Role of Microglia and Astrocytes |date=28 December 2004 | veditors = Aschner M, Costa LG | title = The Role of Glia in Neurotoxicity | edition = 2nd |pages=283–298 |publisher=CRC Press |doi=10.1201/9781420039740-21 |isbn=978-0-429-12860-8 }}</ref>{{Better source needed|reason=Not very recent|date=December 2022}}

In 2024, scientists shared research on their findings of ancient migration to northern Europe from the [[Yamnaya culture|Yamnaya area of culture]],<ref>{{cite journal |vauthors = Allentoft ME, Sikora M, Refoyo-Martínez A, Irving-Pease EK, Fischer A, Barrie W, Ingason A, Stenderup J, Sjögren KG, Pearson A, Sousa da Mota B, Schulz Paulsson B, Halgren A, Macleod R, Jørkov ML, Demeter F, Sørensen L, Nielsen PO, Henriksen RA, Vimala T, McColl H, Margaryan A, Ilardo M, Vaughn A, Fischer Mortensen M, Nielsen AB, Ulfeldt Hede M, Johannsen NN, Rasmussen P, Vinner L, Renaud G, Stern A, Jensen TZ, Scorrano G, Schroeder H, Lysdahl P, Ramsøe AD, Skorobogatov A, Schork AJ, Rosengren A, Ruter A, Outram A, Timoshenko AA, Buzhilova A, Coppa A, Zubova A, Silva AM, Hansen AJ, Gromov A, Logvin A, Gotfredsen AB, Henning Nielsen B, González-Rabanal B, Lalueza-Fox C, McKenzie CJ, Gaunitz C, Blasco C, Liesau C, Martinez-Labarga C, Pozdnyakov DV, Cuenca-Solana D, Lordkipanidze DO, En'shin D, Salazar-García DC, Price TD, Borić D, Kostyleva E, Veselovskaya EV, Usmanova ER, Cappellini E, Brinch Petersen E, Kannegaard E, Radina F, Eylem Yediay F, Duday H, Gutiérrez-Zugasti I, Merts I, Potekhina I, Shevnina I, Altinkaya I, Guilaine J, Hansen J, Aura Tortosa JE, Zilhão J, Vega J, Buck Pedersen K, Tunia K, Zhao L, Mylnikova LN, Larsson L, Metz L, Yepiskoposyan L, Pedersen L, Sarti L, Orlando L, Slimak L, Klassen L, Blank M, González-Morales M, Silvestrini M, Vretemark M, Nesterova MS, Rykun M, Rolfo MF, Szmyt M, Przybyła M, Calattini M, Sablin M, Dobisíková M, Meldgaard M, Johansen M, Berezina N, Card N, Saveliev NA, Poshekhonova O, Rickards O, Lozovskaya OV, Gábor O, Uldum OC, Aurino P, Kosintsev P, Courtaud P, Ríos P, Mortensen P, Lotz P, Persson P, Bangsgaard P, de Barros Damgaard P, Vang Petersen P, Martinez PP, Włodarczak P, Smolyaninov RV, Maring R, Menduiña R, Badalyan R, Iversen R, Turin R, Vasilyev S, Wåhlin S, Borutskaya S, Skochina S, Sørensen SA, Andersen SH, Jørgensen T, Serikov YB, Molodin VI, Smrcka V, Merts V, Appadurai V, Moiseyev V, Magnusson Y, Kjær KH, Lynnerup N, Lawson DJ, Sudmant PH, Rasmussen S, Korneliussen TS, Durbin R, Nielsen R, Delaneau O, Werge T, Racimo F, Kristiansen K, Willerslev E | title=Population genomics of post-glacial western Eurasia |doi-access=free|journal=Nature |date=11 January 2024 |volume=625 |issue=7994 |pages=301–311 |doi=10.1038/s41586-023-06865-0| pmid=38200295 | pmc=10781627 | bibcode=2024Natur.625..301A }}</ref> tracing MS-risk gene variants dating back around 5,000 years.<ref>{{Cite news |vauthors=Johnson CY |date=2024-01-10 |title=Ancient DNA helps trace multiple sclerosis origins in European descendants |url=https://www.washingtonpost.com/science/2024/01/10/ancient-dna-multiple-sclerosis-european-ancestry/ |access-date=2024-01-11 |newspaper=Washington Post |archive-date=17 August 2024 |archive-url=https://web.archive.org/web/20240817130847/https://www.washingtonpost.com/science/2024/01/10/ancient-dna-multiple-sclerosis-european-ancestry/ |url-status=live }}</ref><ref>{{Cite web |vauthors=Roxby P |date=10 January 2024 |title=Scientists crack mystery of how MS gene spread |url=https://www.bbc.com/news/health-67917294 |access-date=2024-01-11 |website=BBC News |language=en-GB |archive-date=11 January 2024 |archive-url=https://web.archive.org/web/20240111083346/https://www.bbc.com/news/health-67917294 |url-status=live }}</ref> The MS-risk gene variants protected ancient cattle herders from animal diseases,<ref>{{cite bioRxiv |vauthors= Barrie W, Yang Y, Irving-Pease E, Attfield KE, Scorrano G, Jensen LT, Armen AP, Dimopoulos EA, Stern A, Refoyo-Martinez A, Pearson A | title =  Elevated genetic risk for multiple sclerosis originated in Steppe Pastoralist populations.  |date=October 6, 2023 |biorxiv=10.1101/2023.10.06.561165|quote=Our findings also support the interpretation of increased pathogen pressure as a driver of positive selection on immunogenetic variants associated with risk of the autoimmune disease multiple sclerosis in Steppe populations around 5,000 years ago[[doi:10.1101/2022.09.23.509097|[59]<nowiki/>]]}}</ref> but modern lifestyles, diets and better hygiene, have allowed the gene to develop, resulting in the higher risk of MS today.<ref>{{Cite web|url=https://www.nationalmssociety.org/About-the-Society/News/Novel-Study-Suggests-that-MS-was-Brought-to-Northe|title=Novel Study Suggests that MS was Brought to Northern Europe 5,000 Years Ago|date=10 January 2024|work=National MS Society|access-date=11 January 2024|archive-date=11 January 2024|archive-url=https://web.archive.org/web/20240111083629/https://www.nationalmssociety.org/About-the-Society/News/Novel-Study-Suggests-that-MS-was-Brought-to-Northe|url-status=live}}</ref>