Mucosal-associated invariant T cells from induced pluripotent stem cells: A novel approach for modeling human diseases

Table 1 Clinical relevance of mucosal-associated invariant T cells

Disease categories	Diseases or status	Features relevant to the diseases	Ref.
Infectious diseases	Pneumopathy	Decrease in frequency and absolute number of MAIT cells in peripheral blood	[16]
	Tuberculosis (Mycobacterium tuberculosis)	Decrease in frequency and absolute number of MAIT cells in peripheral blood Enriched in the lung	[16,37,92]
	HIV/AIDS (opportunistic infection)	Decrease in frequency of MAIT cells in peripheral blood, guts, and lymph nodes Failure of recovery of blood MAIT cells with successful cART Long-term cART restore colonic but not blood MAIT cell levels MAIT cells are depleted but retain functionality	[38-43,93,94]
	Sepsis (severe bacterial infection)	Decrease in frequency and absolute number of MAIT cells in peripheral blood of patients	[95]
	P. aeruginosa infection with cystic fibrosis	Decrease in frequency of MAIT cells in peripheral blood of cystic fibrosis patients with P. aeruginosa infection	[96]
	Cholera (Vibrio cholera O1)	Activation of MAIT cells in the acute phase No change of blood MAIT cell frequency in adult patients, but persistently decreased in child patients	[97]
Autoimmune diseases	Multiple sclerosis	Accumulation of MAIT cells in the central nervous system lesions Decrease in frequency of MAIT cells in peripheral blood	[44-46,48]
		Increased CD161high CD8+ T cells in peripheral blood	[98]
	Chronic inflammatory demyelinating polyneuropathy	Accumulation of MAIT cells in the peripheral nerves	[44]
	Psoriatic and rheumatoid arthritis Rheumatoid arthritis	Enrichment of CD161high CD8+ T cells in the joints and secretion of IL-17 from those cells	[99]
	Inflammatory bowel disease	Decrease in frequency and absolute number of MAIT cells (in particularly, in CD8+ and DN subsets) in peripheral blood	[53]
		Increased MAIT cell levels in the synovial fluid Decrease in CD8+ MAIT cells in peripheral blood of CD and UC patients Accumulation of MAIT cells in the inflamed ileon of patients with CD Reduced IFN-γ production in CD patients and increased IL-17 production in CD and UC patients	[49]
		Fewer MAIT cells in in the inflamed ileon of patients with CD and UC Increased apoptosis in MAIT cells	[100]
	Psoriasis	MAIT cells reside in not only the dermis of patients but also that of health donors. MAIT cells may contribute IL-17 production in the dermis of patients	[51]
	Celiac disease	Decrease in frequency of MAIT cells in peripheral blood and guts of adult and pediatric patients	[52]
	Systemic lupus erythematosus	Decrease in frequency and absolute number of MAIT cells (in particularly, in CD8+ and DN subsets) in peripheral blood Reduced IFN-γ production Elevated expression of PD-1 in MAIT cells	[53]
Inflammatory diseases	Asthma	Decrease in frequency of MAIT cells in blood, sputum, and endobronchial biopsy	[101]
	Diabetes type 2/obesity	Decrease in frequency of MAIT cells in peripheral blood Circulating MAIT cells display an activate phenotype MAIT cells are more abundant in adipose tissue	[55,56]
	Acute cholecystitis	Decrease in frequency and absolute number of MAIT cells in peripheral blood	[102]
	Fibromyalgia syndrome vs Spondyloarthritis vs Rheumatoid arthritis	Defined analysis of MAIT cell phenotype among three diseases that exhibit a similar clinical manifestation Decrease in frequency of MAIT cells in three diseases Three diseases are able to distinguish by surface marker expression	[57]
Tissue transplant	Cutaneous acute graft-vs-host disease	Infiltration of CD8+ T cells, CD161+, CCR6+, RORγt+ in the epidermis and dermis of patients with GVHD	[103]
	Hemodialyzed and kidney transplant	Decrease in frequency of MAIT cells in peripheral blood Implication for the susceptibility to infections in the patients	[104]
Tumors	Kidney and brain tumors	Presence of MAIT cells in tumors	[58]
Physiological change	Fetus	Rare and immature in the thymus, spleen, mesenteric lymph nodes Mature and enriched in the guts, liver, and lung	[29]
	Neonate/infant	Naïve phenotype at birth. Acquisition of effector/memory phenotype and increase in frequency and number with age	[11,30]
	Adult	Maximum levels in the third and fourth decenniums Higher amounts in females with reproductive age than in males	[30]
	Aging	Decrease in CD8+ MAIT cells and increase in CD4+ MAIT cells with age Th2 shift in cytokine profile in elderly	[22,30]

CD: Crohn’s disease; UC: Ulcerative colitis; MAIT: Mucosal-associated invariant T; HIV: Human immunodeficiency virus; AIDS: Acquired immunodeficiency syndrome; P. aeruginosa: Pseudomonas aeruginosa.

Table 2 Mice used in study for mucosal-associated invariant T cells

	Genotype	Characteristics	Ref.
Knockout mice	MR1-/-	Impaired development of MAIT cells	[79]
Transgenic mice	Vα19 iTCR Tg	Enriched MAIT cells	[17,78-80]
	Vβ6 Vβ8 Tg	Increase of MAIT cells	[17]

MAIT: Mucosal-associated invariant T; iTCR: Invariant T cell receptor.

Table 3 Mucosal-associated invariant T cells in the diseases

Category	Mouse strains	Disease model	Phenotype	Ref.
Bacterial infection	MR1-/- Vα19 iTCR Tg Vβ6 Vβ8 Tg	Escherichia coliMicobacterium abcessus	Increase in the bacterial burden Repression of the bacterial burden	[16]
	MR1-/-	Klebsiella pneumoniae	Increased susceptibility to K. pneumoniae infection	[36]
	MR1-/-	Mycobacterium bovis BCG	Enhanced bacterial growth at the early stage of infection	[35]
		Francisella tularensis	Delayed adaptive immune reaction	[34]
Autoimmune diseases	Vα19 iTCR Tg	Experimental autoimmune encephalomyelitis (model of MS)	Suppressed disease induction and progression	[78]
	MR1-/-	Collagen-induced arthritis (model of rheumatoid arthritis)	Improved CIA score	[86]
	Adoptive transfer Jα33+ MAIT cells into BALB/c	TNBS induced colitis	Improved disease index	[105]
	B10.RIII	Spondyloarthropathy by IL-23	Enthesitis induced by IL-22 produced from IL-23R+RORγt+CD4-CD8- T cells (MAIT cells?) in the entheses	[91]
Others	Vα19 iTCR Tg NOD	Non-obese diabetes	Delayed disease onset	[106]
	Vα19 iTCR Tg	Delayed-type hypersensitivity to sheep erythrocytes (type IV allergy)	Suppression of the disease	[106]

MAIT: Mucosal-associated invariant T; IL: Interleukin; CIA: Collagen-induced arthritis; iTCR: Invariant T cell receptor.