Tissue-resident memory-like ILCs: innate counterparts of T_RM cells

Abstract

Innate lymphoid cells (ILCs) are defined as lymphocytes that lack RAG recombinase and do not express diverse antigen receptors; however, recent studies have revealed the adaptive features of ILCs. Mouse cytome-galovirus (MCMV)- and cytokine-induced memory natu-ral killer (NK) cells circulate in the blood and are referred to as conventional memory NK cells. In contrast, virus- and hapten-induced memory NK cells, hapten-induced memory ILC1s, and cytokine-induced memory-like ILC2s exhibit long-term residency in the liver or lung, and are referred to as tissue-resident memory ILCs. Considering their similar migration patterns and mem- ory potential, tissue-resident memory ILCs could be regarded as innate counterparts of resident memory T (T_RM) cells. Both tissue-resident memory ILCs and T_RM cells share common characteristics in terms of dynam- ics, phenotype, and molecular regulation. The emer-gence of ILC memory expands the basic biology of ILCs and prompts us to re-examine their functions in disease progression. This review discusses the evidence sup-porting tissue-resident memory NK cells and other memory ILC subsets, compares them with TRM cells, and highlights key unsolved questions in this emerging field.

Keywords

tissue-residency / innate lymphoid cells / immunological memory / TRM cells

References

[1] Adachi T, Kobayashi T,Sugihara E, Yamada T, Ikuta K, Pittaluga S, Saya H, Amagai M, Nagao K (2015) Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma. Nat Med 21:1272

[2] Andreotti JP, Paiva AE, Prazeres PHDM, Guerra DAP, Silva WN, Vaz RS, Mintz A, Birbrair A (2018) The role of natural killer cells in the uterine microenvironment during pregnancy. Cell Mol Immunol 15:941–943

[3] Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296:1323–1326

[4] Arnon TI, Achdout H, Lieberman N, Gazit R, Gonen-Gross T, Katz G, Bar-Ilan A, Bloushtain N, Lev M, Joseph A (2004) The mechanisms controlling the recognition of tumor- and virus- infected cells by NKp46. Blood 103:664–672

[5] Artis D, Spits H (2015) The biology of innate lymphoid cells. Nature 517:293–301

[6] Aw Yeang HX, Piersma SJ, Lin Y, Yang L, Malkova ON, Miner C, Krupnick AS, Chapman WC, Yokoyama WM (2017) Cutting edge: human CD49e− NK cells are tissue resident in the liver. J Immunol 198:1417–1422

[7] Bergsbaken T, Bevan MJ (2015) Proinflammatory microenviron ments within the intestine regulate the differentiation of tissue- resident CD8+ T cells responding to infection. Nat Immunol 16:406

[8] Bergsbaken T, Bevan MJ, Fink PJ (2017) Local inflammatory cues regulate differentiation and persistence of CD8+ tissue-resident memory T cells. Cell Rep 19:114–124

[9] Brown MG, Dokun AO, Heusel JW, Smith HRC, Beckman DL, Blattenberger EA, Dubbelde CE, Stone LR, Scalzo AA, Yokoyama WM (2001) Vital involvement of a natural killer cell activation receptor in resistance to viral infection. Science 292:934–937

[10] Carbone T, Nasorri F, Pennino D, Eyerich K, Foerster S, Cifaldi L, Traidl-Hoffman C, Behrendt H, Cavani A (2010) CD56highCD16 CD62L-NK cells accumulate in allergic contact dermatitis and contribute to the expression of allergic responses. J Immunol 184:1102–1110

[11] Cella M, Fuchs A, Vermi W, Facchetti F, Otero K, Lennerz JKM, Doherty JM, Mills JC, Colonna M (2008) A human natural killer cell subset provides an innate source of IL-22 for mucosal immunity. Nature 457:722

[12] Cepek KL, Shaw SK, Parker CM, Russell GJ, Morrow JS, Rimm DL, Brenner MB (1994) Adhesion between epithelial cells and T lymphocytes mediated by E-cadherin and the αEβ7 integrin. Nature 372:190–193

[13] Cerwenka A, Lanier LL (2016) Natural killer cell memory in infection, inflammation and cancer. Nat Rev Immunol 16:112

[14] Cheuk S, Schlums H, Gallais Sérézal I, Martini E, Chiang SC, Marquardt N, Gibbs A, Detlofsson E, Introini A, Forkel M (2017) CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin. Immunity 46:287–300

[15] Cichocki F, Wu CY, Zhang B, Felices M, Tesi B, Tuininga K, Dougherty P, Taras E, Hinderlie P, Blazar BR (2018) ARID5B regulates metabolic programming in human adaptive NK cells. J Exp Med 215:2379–2395

[16] Cong J, Wang X, Zheng X, Wang D, Fu B, Sun R, Tian Z, Wei H (2018) Dysfunction of natural killer cells by FBP1-induced inhibition of glycolysis during lung cancer progression. Cell Metab 28(243–255):e245

[17] Cooper MA (2018) Natural killer cells might adapt their inhibitory receptors for memory. Proc Natl Acad Sci 115:11357

[18] Cooper MA, Elliott JM, Keyel PA, Yang L, Carrero JA, Yokoyama WM (2009) Cytokine-induced memory-like natural killer cells. Proc Natl Acad Sci USA 106:1915–1919

[19] Cortez VS, Cervantes-Barragan L, Robinette ML, Bando JK, Wang Y, Geiger TL, Gilfillan S, Fuchs A, Vivier E, Sun JC (2016) Transforming growth factor-β signaling guides the differentiation of innate lymphoid cells in salivary glands. Immunity 44:1127–1139

[20] Cuff AO, Robertson FP, Stegmann KA, Pallett LJ, Maini MK, Davidson BR, Male V (2016) Eomeshi NK cells in human liver are long-lived and do not recirculate but can be replenished from the circulation. J Immunol 197:4283–4291

[21] Cui G, Staron MM, Gray SM, Ho PC, Amezquita RA, Wu J, Kaech SM (2015) IL-7-Induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity. Cell 161:750–761

[22] Cupedo T, Crellin NK, Papazian N, Rombouts EJ, Weijer K, Grogan JL, Fibbe WE, Cornelissen JJ, Spits H (2008) Human fetal lymphoid tissue-inducer cells are interleukin 17-producing pre cursors to RORC+ CD127+ natural killer-like cells. Nat Immunol 10:66

[23] Diefenbach A, Colonna M, Koyasu S (2014) Development, differen tiation, and diversity of innate lymphoid cells. Immunity 41:354–365

[24] Eberl G, Colonna M, Di Santo JP, McKenzie AN (2015) Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science 348:aaa6566

[25] Fernandez-Ruiz D, Ng Wei Y, Holz LE, Ma Joel Z, Zaid A, Wong Yik C, Lau Lei S, Mollard V, Cozijnsen A, Collins N (2016) Liver- resident memory CD8+ T cells form a front-line defense against malaria liver-stage infection. Immunity 45:889–902

[26] Filipovic I, Chiossone L, Vacca P, Hamilton RS, Ingegnere T, Doisne J-M, Hawkes DA, Mingari MC, Sharkey AM, Moretta L (2018) Molecular definition of group 1 innate lymphoid cells in the mouse uterus. Nat Commun 9:4492

[27] Firth MA, Madera S, Beaulieu AM, Gasteiger G, Castillo EF, Schluns KS, Kubo M, Rothman PB, Vivier E, Sun JC (2013) Nfil3 independent lineage maintenance and antiviral response of natural killer cells. J Exp Med 210:2981–2990

[28] Fu B, Zhou Y, Ni X, Tong X, Xu X, Dong Z, Sun R, Tian Z, Wei H (2017) Natural killer cells promote fetal development through the secretion of growth-promoting factors. Immunity 47(1100–1113): e1106

[29] Fuchs A, Vermi W, Lee Jacob S, Lonardi S, Gilfillan S, Newberry Rodney D, Cella M, Colonna M (2013) Intraepithelial type 1 innate lymphoid cells are a unique subset of IL-12- and IL-15 responsive IFN-γ-producing cells. Immunity 38:769–781

[30] Gamliel M, Goldman-Wohl D, Isaacson B, Gur C, Stein N, Yamin R, Berger M, Grunewald M, Keshet E, Rais Y (2018) Trained memory of human uterine NK cells enhances their function in subsequent pregnancies. Immunity 48:951–962.e955

[31] Gasteiger G, Fan X, Dikiy S, Lee SY, Rudensky AY (2015) Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science 350:981–985

[32] Gillard GO, Bivas-Benita M, Hovav A-H, Grandpre LE, Panas MW, Seaman MS, Haynes BF, Letvin NL (2011) Thy1+ Nk cells from vaccinia virus-primed mice confer protection against vaccinia virus challenge in the absence of adaptive lymphocytes. PLOS Pathog 7:e1002141

[33] Hammer Q, Ruckert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A (2018) Peptide- specific recognition of human cytomegalovirus strains controls adaptive natural killer cells. Nat Immunol 19:453–463

[34] Hudspeth K, Donadon M, Cimino M, Pontarini E, Tentorio P, Preti M, Hong M, Bertoletti A, Bicciato S, Invernizzi P (2016) Human liver-resident CD56(bright)/CD16(neg) NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways. J Autoimmun 66:40–50

[35] Hydes T, Noll A, Salinas-Riester G, Abuhilal M, Armstrong T, Hamady Z, Primrose J, Takhar A, Walter L, Khakoo SI (2017) IL 12 and IL-15 induce the expression of CXCR6 and CD49a on peripheral natural killer cells. Immun Inflamm Dis 6:34–46

[36] Jiang X, Clark RA, Liu L, Wagers AJ, Fuhlbrigge RC, Kupper TS (2012) Skin infection generates non-migratory memory CD8+ T (RM) cells providing global skin immunity. Nature 483:227–231

[37] Kamimura Y, Lanier LL (2015) Homeostatic control of memory cell progenitors in the natural killer cell lineage. Cell Rep 10:280–291

[38] Kaplan DH, Igyarto BZ, Gaspari AA (2012) Early immune events in the induction of allergic contact dermatitis. Nat Rev Immunol 12:114–124

[39] Klose CSN, Flach M, Mohle L, Rogell L, Hoyler T, Ebert K, Fabiunke C, Pfeifer D, Sexl V, Fonseca-Pereira D (2014) Differenti ation of type 1 ILCs from a common progenitor to all helper-like innate lymphoid cell lineages. Cell 157:340–356

[40] Laidlaw Brian J, Zhang N, Marshall Heather D, Staron Mathew M, Guan T, Hu Y, Cauley Linda S, Craft J, Kaech Susan M (2014) CD4+ T cell help guides formation of CD103+ lung-resident memory CD8+ T cells during influenza viral infection. Immunity 41:633–645

[41] Lau CM, Adams NM, Geary CD, Weizman OE, Rapp M, Pritykin Y, Leslie CS, Sun JC (2018) Epigenetic control of innate and adaptive immune memory. Nat Immunol 19:963–972

[42] Li T, Wang J, Wang Y, Chen Y, Wei H, Sun R, Tian Z (2017) Respiratory influenza virus infection induces memory-like liver NK cells in mice. J Immunol 198:1242–1252

[43] Liang B, Hara T, Wagatsuma K, Zhang J, Maki K, Miyachi H, Kitano S, Yabe-Nishimura C, Tani-Ichi S, Ikuta K (2012) Role of hepatocyte-derived IL-7 in maintenance of intrahepatic NKT cells and T cells and development of B cells in fetal liver. J Immunol 189:4444–4450

[44] Lopez-Verges S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, Houchins JP, Miller S, Kang SM, Norris PJ (2011) Expansion of a unique CD57(+)NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci USA 108:14725–14732

[45] Mackay LK, Braun A, Macleod BL, Collins N, Tebartz C, Bedoui S, Carbone FR, Gebhardt T (2015a) Cutting edge: CD69 interfer ence with sphingosine-1-phosphate receptor function regulates peripheral T cell retention. J Immunol 194:2059–2063

[46] Mackay LK, Minnich M, Kragten NAM, Liao Y, Nota B, Seillet C, Zaid A, Man K, Preston S, Freestone D (2016) Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352:459–463

[47] Mackay LK, Rahimpour A, Ma JZ, Collins N, Stock AT, Hafon M-L, Vega-Ramos J, Lauzurica P, Mueller SN, Stefanovic T (2013) The developmental pathway for CD103+CD8+ tissue- resident memory T cells of skin. Nat Immunol 14:1294

[48] Mackay LK, Wynne-Jones E, Freestone D, Pellicci DG, Mielke LA, Newman DM, Braun A, Masson F, Kallies A, Belz GT (2015b) T-box transcription factors combine with the cytokines TGF-beta and IL-15 to control tissue-resident memory t cell fate. Immunity 43:1101–1111

[49] Majewska-Szczepanik M, Paust S, von Andrian UH, Askenase PW, Szczepanik M (2013) Natural killer cell-mediated contact sensi tivity develops rapidly and depends on interferon-alpha, inter- feron-gamma and interleukin-12. Immunology 140:98–110

[50] Marquardt N, Béziat V, Nyström S, Hengst J, Ivarsson MA, Kekäläinen E, Johansson H, Mjösberg J, Westgren M, Lankisch TO (2015) Cutting edge: identification and characterization of human intrahepatic CD49a+ NK Cells. J Immunol 194:2467–2471

[51] Martinez-Gonzalez I, Matha L, Steer CA, Ghaedi M, Poon GF, Takei F (2016) Allergen-experienced group 2 innate lymphoid cells acquire memory-like properties and enhance allergic lung inflammation. Immunity 45:198–208

[52] Martinez-Gonzalez I,Matha L, Steer CA, Takei F (2017) Immuno logical memory of group 2 innate lymphoid cells. Trends Immunol 38:423–431

[53] Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J-I, Ohtani M, Fujii H, Koyasu S (2009) Innate production of TH2 cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature 463:540

[54] Mueller SN, Gebhardt T, Carbone FR, Heath WR (2013) Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol 31:137–161

[55] Mueller SN, Mackay LK (2015) Tissue-resident memory T cells: local specialists in immune defence. Nat Rev Immunol 16:79

[56] Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TKA, Bucks C, Kane CM, Fallon PG, Pannell R (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367

[57] O’Leary JG, Goodarzi M, Drayton DL, von Andrian UH (2006) T cell and B cell-independent adaptive immunity mediated by natural killer cells. Nat Immunol 7:507–516

[58] O’Sullivan TE, Sun JC, Lanier LL (2015) Natural killer cell memory. Immunity 43:634–645

[59] O’Brien KL, Finlay DK (2019) Immunometabolism and natural killer cell responses. Nat Rev Immunol 19:282–290

[60] Pahl JHW, Cerwenka A, Ni J (2018) Memory-like NK cells: remembering a previous activation by cytokines and NK cell receptors. Front Immunol 9:2796

[61] Paust S, Gill HS, Wang BZ, Flynn MP, Moseman EA, Senman B, Szczepanik M, Telenti A, Askenase PW, Compans RW (2010) Critical role for the chemokine receptor CXCR6 in NK cell- mediated antigen-specific memory of haptens and viruses. Nat Immunol 11:1127–1135

[62] Peng H, Jiang X, Chen Y, Sojka DK, Wei H, Gao X, Sun R, Yokoyama WM, Tian Z (2013a) Liver-resident NK cells confer adaptive immunity in skin-contact inflammation. J Clin Invest 123:1444–1456

[63] Peng H, Sun R (2017) Liver-resident NK cells and their potential functions. Cell Mol Immunol 14:890

[64] Peng H, Sun R, Tang L, Wei H, Tian Z (2013b) CD62L is critical for maturation and accumulation of murine hepatic NK cells in response to viral infection. J Immunol 190:4255

[65] Rapp M, Wiedemann GM, Sun JC (2018) Memory responses of innate lymphocytes and parallels with T cells. Semin Immuno pathol 40:343–355

[66] Robinette ML, Bando JK, Song W, Ulland TK, Gilfillan S, Colonna M (2017) IL-15 sustains IL-7R-independent ILC2 and ILC3 devel opment. Nat Commun 8:14601

[67] Romee R, Schneider SE, Leong JW, Chase JM, Keppel CR, Sullivan RP, Cooper MA, Fehniger TA (2012) Cytokine activation induces human memory-like NK cells. Blood 120:4751–4760

[68] Salimi M, Barlow JL, Saunders SP, Xue L, Gutowska-Owsiak D, Wang X, Huang L-C, Johnson D, Scanlon ST, McKenzie ANJ (2013) A role for IL-25 and IL-33–driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med 210:2939

[69] Sanos SL, Bui VL, Mortha A, Oberle K, Heners C, Johner C, Diefenbach A (2008) RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-produc ing NKp46+ cells. Nat Immunol 10:83

[70] Satoh-Takayama N, Vosshenrich CAJ, Lesjean-Pottier S, Sawa S, Lochner M, Rattis F, Mention J-J, Thiam K, Cerf-Bensussan N, Mandelboim O (2008) Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29:958–970

[71] Schenkel Jason M, Masopust D (2014) Tissue-resident memory T cells. Immunity 41:886–897

[72] Sheridan Brian S, Pham Q-M, Lee Y-T, Cauley Linda S, Puddington L, Lefrançois L (2014) Oral infection drives a distinct population of intestinal resident memory CD8+ T cells with enhanced protective function. Immunity 40:747–757

[73] Shiow LR, Rosen DB, Brdičková N, Xu Y, An J, Lanier LL, Cyster JG, Matloubian M (2006) CD69 acts downstream of interferon-α/β to inhibit S1P1 and lymphocyte egress from lymphoid organs. Nature 440:540–544

[74] Skon CN, Lee J-Y, Anderson KG, Masopust D, Hogquist KA, Jameson SC (2013) Transcriptional downregulation of S1pr1 is required for the establishment of resident memory CD8+ T cells. Nat Immunol 14:1285–1293

[75] Smolders J, Heutinck KM, Fransen NL, Remmerswaal EBM, Hombrink P, ten Berge IJM, van Lier RAW, Huitinga I, Hamann J (2018) Tissue-resident memory T cells populate the human brain. Nat Commun 9:4593

[76] Sojka DK, Plougastel-Douglas B, Yang L, Pak-Wittel MA, Artyomov MN, Ivanova Y, Zhong C, Chase JM, Rothman PB, Yu J (2014) Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells. Elife 3: e01659

[77] Sojka DK, Yang L, Plougastel-Douglas B, Higuchi DA, Croy BA, Yokoyama WM (2018) Cutting edge: local proliferation of uterine tissue-resident NK cells during decidualization in mice. J Immunol 201:2551–2556

[78] Stegmann KA, Robertson F, Hansi N, Gill U, Pallant C, Christo phides T, Pallett LJ, Peppa D, Dunn C, Fusai G (2016) CXCR6 marks a novel subset of T-betloEomeshi natural killer cells residing in human liver. Sci Rep 6:26157

[79] Sun JC, Beilke JN, Lanier LL (2009) Adaptive immune features of natural killer cells. Nature 457:557–561

[80] Tan Z, Liu Q, Jiang R, Lv L, Shoto SS, Maillet I, Quesniaux V, Tang J, Zhang W, Sun B (2018) Interleukin-33 drives hepatic fibrosis through activation of hepatic stellate cells. Cell Mol Immunol 15:388–398

[81] Tang L, Peng H, Zhou J, Chen YY, Wei HM, Sun R, Yokoyama WM, Tian ZG (2016) Differential phenotypic and functional properties of liver-resident NK cells and mucosal ILC1s. J Autoimmun 67:29–35

[82] Teijaro JR, Turner D, Pham Q, Wherry EJ, Lefrançois L, Farber DL (2011) Cutting edge: tissue-retentive lung memory CD4 T cells mediate optimal protection to respiratory virus infection. J Im munol 187:5510

[83] van den Boorn JG, Jakobs C, Hagen C, Renn M, Luiten RM, Melief CJ, Tuting T, Garbi N, Hartmann G, Hornung V (2016) Inflam masome-dependent induction of adaptive NK cell memory. Immunity 44:1406–1421

[84] Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP, Eberl G, Koyasu S, Locksley RM, McKenzie ANJ, Mebius RE (2018) Innate lymphoid cells: 10 years on. Cell 174:1054–1066

[85] Wakim LM, Woodward-Davis A, Bevan MJ (2010) Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Natl Acad Sci USA 107:17872

[86] Wang X, Peng H, Cong J, Wang X, Lian Z, Wei H, Sun R, Tian Z (2018) Memory formation and long-term maintenance of IL 7Ralpha(+) ILC1s via a lymph node-liver axis. Nat Commun 9:4854

[87] Wang X, Peng H, Tian Z (2019) Innate lymphoid cell memory. Cell Mol Immunol 16:423–429

[88] Weiskirchen R, Tacke F (2017) Interleukin-33 in the pathogenesis of liver fibrosis: alarming ILC2 and hepatic stellate cells. Cell Mol Immunol 14:143

[89] Weizman OE, Adams NM, Schuster IS, Krishna C, Pritykin Y, Lau C, Degli-Esposti MA, Leslie CS, Sun JC, O’Sullivan TE (2017) ILC1 confer early host protection at initial sites of viral infection. Cell 171(795–808):e712

[90] Wight A, Mahmoud AB, Scur M, Tu MM, Rahim MMA, Sad S, Makrigiannis AP (2018) Critical role for the Ly49 family of class I MHC receptors in adaptive natural killer cell responses. Proc Natl Acad Sci USA 115:11579–11584

[91] Wittig O, Paez-Cortez J, Cardier JE (2010) Liver sinusoidal endothelial cells promote B lymphopoiesis from primitive hematopoietic cells. Stem Cells Dev 19:341–350

[92] Wu LS-H, Wang J-Y (2018) Warm up, cool down, and tearing apart in NK cell memory. Cell Mol Immunol 15:1095–1097

[93] Zaid A, Hor JL, Christo SN, Groom JR, Heath WR, Mackay LK, Mueller SN (2017) Chemokine receptor-dependent control of skin tissue-resident memory T cell formation. J Immunol 199:2451

[94] Zhang LH, Shin JH, Haggadone MD, Sunwoo JB (2016) The aryl hydrocarbon receptor is required for the maintenance of liver- resident natural killer cells. J Exp Med 213:2249–2257

[95] Zhang Q-F, Yin W-W, Xia Y, Yi Y-Y, He Q-F, Wang X, Ren H, Zhang D-Z (2017) Liver-infiltrating CD11b−CD27− NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression. Cell Mol Immunol 14:819

[96] Zundler S, Becker E, Spocinska M, Slawik M, Parga-Vidal L, Stark R, Wiendl M, Atreya R, Rath T, Leppkes M (2019) Hobit- and Blimp-1-driven CD4+ tissue-resident memory T cells control chronic intestinal inflammation. Nat Immunol 20:288–300

RIGHTS & PERMISSIONS

The Author(s)