Abstract

Innate lymphoid cells (ILC) is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer) and lymphoid tissue inducer T cells (LTi), which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-γ, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell – TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22) – which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22) cells or NK receptor-positive (LTi NKR+) LTi cells. Fourth population of ILC cells are ILC17 – producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2), nuocyte, innate type 2 helper cells (IH2) and multi-potent progenitor type 2 cells (MPPtype2). Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors – as direct regulation factors, such as the family of lymphocytes T.

References

• 1. Arase H., Lanier L.L.: Virus-driven evolution of natural killer cellreceptors. Microbes Infect., 2002; 4: 1505-1512
  Google Scholar
• 2. Ashkar A.A., Di Santo J.P., Croy B.A.: Interferon gamma contributesto initiation of uterine vascular modification, decidual integrity, anduterine natural killer cell maturation during normal murine pregnancy.J. Exp. Med., 2000; 192: 259-270
  Google Scholar
• 3. Biron C.A., Nguyen K.B., Pien G.C., Cousens L.P., Salazar-Mather T.P.:Natural killer cells in antiviral defense: function and regulation by innatecytokines. Annu. Rev. Immunol., 1999; 17: 189-220
  Google Scholar
• 4. Blaho V.A., Buczynski M.W., Dennis E.A., Brown C.R.: Cyclooxygenase-1orchestrates germinal center formation and antibody class-switchvia regulation of IL-17. J. Immunol., 2009; 183: 5644-5653
  Google Scholar
• 5. Bouskra D., Brézillon C., Bérard M., Werts C., Varona R., Boneca I.G.,Eberl G.: Lymphoid tissue genesis induced by commensals throughNOD1 regulates intestinal homeostasis. Nature, 2008; 456: 507-510
  Google Scholar
• 6. Buonocore S., Ahern P.P., Uhlig H.H., Ivanov I.I., Littman D.R., MaloyK.J., Powrie F.: Innate lymphoid cells drive interleukin-23-dependentinnate intestinal pathology. Nature, 2010; 464: 1371-1375
  Google Scholar
• 7. Cella M., Fuchs A., Vermi W., Facchetti F., Otero K., Lennerz J.K., DohertyJ.M., Mills J.C., Colonna M.: A human natural killer cell subsetprovides an innate source of IL-22 for mucosal immunity. Nature, 2009;457: 722-725
  Google Scholar
• 8. Cella M., Otero K., Colonna M.: Expansion of human NK-22 cells withIL-7, IL-2, and IL-1β reveals intrinsic functional plasticity. Proc. Natl.Acad. Sci. USA, 2010; 107: 10961-10966
  Google Scholar
• 9. Cooper M.A., Fehniger T.A., Caligiuri M.A.: The biology of humannatural killer-cell subsets. Trends Immunol., 2001; 22: 633-640
  Google Scholar
• 10. Crellin N.K., Trifari S., Kaplan C.D., Cupedo T., Spits H.: HumanNKp44+IL-22+ cells and LTi-like cells constitute a stable RORC+ lineagedistinct from conventional natural killer cells. J. Exp. Med., 2010;207: 281-290
  Google Scholar
• 11. Crellin N.K., Trifari S., Kaplan C.D., Satoh-Takayama N., Di SantoJ.P., Spits H.: Regulation of cytokine secretion in human CD127+ LTi-likeinnate lymphoid cells by Toll like receptor 2 Immunity. Immunity.,2010; 33: 752-764
  Google Scholar
• 12. Cupedo T., Crellin N.K., Papazian N., Rombouts E.J., Weijer K., GroganJ.L., Fibbe W.E., Cornelissen J.J., Spits H.: Human fetal lymphoid tissue–inducer cells are interleukin 17-producing precursors to RORC+CD127+natural killer-like cells. Nat. Immunol., 2009; 10: 66-74
  Google Scholar
• 13. Di Santo J.P.: Natural killer cells: diversity in search of a niche. Nat.Immunol., 2008; 9: 473-475
  Google Scholar
• 14. Eberl G. Eberl G., Marmon S., Sunshine M.J., Rennert P.D., Choi Y.,Littman D.R.: An essential function for the nuclear receptor RORγ(t) inthe generation of fetal lymphoid tissue inducer cells. Nat. Immunol.,2004; 5: 64-73
  Google Scholar
• 15. Fallon P.G., Ballantyne S.J., Mangan N.E., Barlow J.L., Dasvarma A.,Hewett D.R., McIlgorm A., Jolin H.E., McKenzie A.N.: Identification ofan interleukin (IL)-25-dependent cell population that provides IL-4,IL-5, and IL-13 at the onset of helminth expulsion. J. Exp. Med., 2006;203: 1105-1116
  Google Scholar
• 16. Fauriat C., Long E.O., Ljunggren H.G., Bryceson Y.T.: Regulation ofhuman NK-cell cytokine and chemokine production by target cell recognition.Blood, 2010; 115: 2167-2176 17 Fort M.M., Cheung J., Yen D., Li J., Zurawski S.M., Lo S., Menon S.,Clifford T., Hunte B., Lesley R., Muchamuel T., Hurst S.D., Zurawski G.,Leach M.W., Gorman D.M.: IL-25 induces IL-4, IL-5, and IL-13 and Th2–associated pathologies in vivo. Immunity, 2001; 15: 985-995
  Google Scholar
• 17. cell effector cytokines in inflammation. Immunity, 2008; 28: 454-467
  Google Scholar
• 18. Gur C., Porgador A., Elboim M., Gazit R., Mizrahi S., Stern-GinossarN., Achdout H., Ghadially H., Dor Y., Nir T., Doviner V., Hershkovitz O.,Mendelson M., Naparstek Y., Mandelboim O.: The activating receptorNKp46 is essential for the development of type 1 diabetes. Nat. Immunol.,2010; 11: 121-128
  Google Scholar
• 19. Hamada H., Hiroi T., Nishiyama Y., Takahashi H., Masunaga Y., HachimuraS., Kaminogawa S., Takahashi-Iwanaga H., Iwanaga T., KiyonoH., Yamamoto H., Ishikawa H.: Identification of multiple isolated lymphoidfollicles on the antimesenteric wall of the mouse small intestine.J. Immunol., 2002; 168: 57-64
  Google Scholar
• 20. Hsu H.C., Yang P.A, Wang J., Wu Q., Myers R., Chen J., Yi J., GuentertT., Tousson A., Stanus A.L., Le T.L., Lorenz R.G., Xu H., Kolls J.K., CarterR.H.: Interleukin 17-producing T helper cells and interleukin 17 orchestrateautoreactive germinal center development in autoimmune BXD2mice. Nat. Immunol., 2008; 9: 166-175
  Google Scholar
• 21. Huntington N.D., Vosshenrich C.A., Di Santo J.P.: Developmental pathwaysthat generate natural-killer-cell diversity in mice and humans.Nat. Rev. Immunol., 2007; 7: 703-714
  Google Scholar
• 22. Hurst S.D., Muchamuel T., Gorman D.M., Gilbert J.M., Clifford T.,Kwan S., Menon S., Seymour B., Jackson C., Kung T.T., Brieland J.K., ZurawskiS.M., Chapman R.W., Zurawski G., Coffman R.L.: New IL-17 familymembers promote Th1 or Th2 responses in the lung: in vivo function ofthe novel cytokine IL-25. J. Immunol., 2002; 169: 443-453
  Google Scholar
• 23. Koyasu S., Moro K.: Natural «helper» cells in the lung: good or badhelp? Immunity, 2012; 36: 317-319
  Google Scholar
• 24. Lane P., Kim M.Y., Withers D., Gaspal F., Bekiaris V., Desanti G.,Khan M., McConnell F., Anderson G.: Lymphoid tissue inducer cellsin adaptive CD4 T cell dependent responses. Semin. Immunol., 2008;20: 159-163
  Google Scholar
• 25. Lanier L.L., Le A.M., Civin C.I., Loken M.R., Phillips J.H.: The relationshipof CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression onhuman peripheral blood NK cells and cytotoxic T lymphocytes. J. Immunol.,1986; 136: 4480-4486
  Google Scholar
• 26. Loza M.J., Zamai L., Azzoni L., Rosati E., Perussia B.: Expression oftype 1 (interferon γ) and type 2 (interleukin-13, interleukin-5) cytokinesat distinct stages of natural killer cell differentiation from progenitorcells. Blood, 2002; 99: 1273-1281
  Google Scholar
• 27. Luci C., Reynders A., Ivanov I.I., Cognet C., Chiche L., Chasson L.,Hardwigsen J., Anguiano E., Banchereau J., Chaussabel D., Dalod M., LittmanD.R., Vivier E., Tomasello E.: Influence of the transcription factor RORγt on the development of NKp46+ cell populations in gut and skin.Nat. Immunol., 2009; 10: 75-82
  Google Scholar
• 28. Mebius R.E.: Organogenesis of lymphoid tissues. Nat. Rev. Immunol.,2003; 3: 292-303
  Google Scholar
• 29. Mebius R.E., Rennert P., Weissman I.L.: Developing lymph nodescollect CD4+CD3−LTβ+ cells that can differentiate to APC, NK cells, andfollicular cells but not T or B cells. Immunity, 1997; 7: 493-504
  Google Scholar
• 30. Mękal A., Trzeciak-Ryczek A., Tokarz-Deptuła B., Deptuła W.: NaturalTh2 (nTh2) cells, interleukin 36 and interleukin 37 – new elements ofinnate immunity. Centr. Eur. J. Immunol., 2011; 36: 113-116
  Google Scholar
• 31. Mękal A., Trzeciak-Ryczek A., Tokarz-Deptuła B., Działo J., DeptułaW.: Nowe elementy odporności wrodzonej. Postępy Biol. Kom., 2011;38: 349-357
  Google Scholar
• 32. Molofsky A.B., Nussbaum J.C., Liang H.E., Van Dyken S.J., Cheng L.E.,Mohapatra A., Chawla A., Locksley R.M.: Innate lymphoid type 2 cellssustain visceral adipose tissue eosinophils and alternatively activatedmacrophages. J. Exp. Med., 2013; 210: 535-549
  Google Scholar
• 33. Moro K., Yamada T., Tanabe M., Takeuchi T., Ikawa T., KawamotoH., Furusawa J., Ohtani M., Fujii H., Koyasu S.: Innate production of TH2cytokines by adipose tissue-associated c-Kit+Sca-1+ lymphoid cells. Nature,2010; 463: 540-544
  Google Scholar
• 34. Neill D.R. Wong S.H., Bellosi A., Flynn R.J., Daly M., Langford T.K.,Bucks C, Kane C.M., Fallon P.G., Pannell R., Jolin H.E., McKenzie A.N.: Nuocytesrepresent a new innate effector leukocyte that mediates type-2immunity. Nature, 2010; 464: 1367-1370
  Google Scholar
• 35. Niedźwiedzka-Rystwej P., Herberg M., Deptuła W.: Biology and roleof NK cells – selected data. Centr. Eur. J. Immunol., 2012; 37: 399-404
  Google Scholar
• 36. Ouyang W., Kolls J.K., Zheng Y.: The biological functions of T helper
  Google Scholar
• 37. Owyang A.M., Zaph C., Wilson E.H., Guild K.J., McClanahan T., MillerH.R., Cua D.J., Goldschmidt M., Hunter C.A., Kastelein R.A., Artis D.:Interleukin 25 regulates type 2 cytokine-dependent immunity and limitschronic inflammation in the gastrointestinal tract. J. Exp. Med.,2006; 203: 843-849
  Google Scholar
• 38. Price A.E. Liang H.E., Sullivan B.M., Reinhardt R.L., Eisley C.J., ErleD.J., Locksley R.M.: Systemically dispersed innate IL-13-expressing cellsin type 2 immunity. Proc. Natl. Acad. Sci. USA, 2010; 107: 11489-11494
  Google Scholar
• 39. Ribeiro V.S., Hasan M., Wilson A., Boucontet L., Pereira P., Lesjean–Pottier S., Satoh-Takayama N., Di Santo J.P., Vosshenrich C.A.: ThymicNK Cells develop independently from T cell precursors. J. Immunol.,2010; 185: 4993-4997
  Google Scholar
• 40. Saenz S.A., Siracusa M. C., Perrigoue J.G., Spencer S.P., Urban J.F.Jr., Tocker J.E., Budelsky A. L., Kleinschek M.A., Kastelein R.A., KambayashiT., Bhandoola A., Artis D: IL25 elicits a multipotent progenitorcell population that promotes TH2 cytokine responses. Nature, 2010;464: 1362-1366
  Google Scholar
• 41. Sanos S.L. Bui V.L., Mortha A., Oberle K., Heners C., Johner C., DiefenbachA.: RORγt and commensal microflora are required for the differentiationof mucosal interleukin 22-producing NKp46+ cells. Nat.Immunol., 2009; 10: 83-91
  Google Scholar
• 42. Satoh-Takayama N., Dumoutier L., Lesjean-Pottier S., Ribeiro V.S.,Mandelboim O., Renauld J.C., Vosshenrich C.A., Di Santo J.P.: The naturalcytotoxicity receptor NKp46 is dispensable for IL-22-mediated innateintestinal immune defense against Citrobacter rodentium. J. Immunol.,2009; 183: 6579-6587
  Google Scholar
• 43. Satoh-Takayama N., Lesjean-Pottier S., Vieira P., Sawa S., Eberl G.,Vosshenrich C.A.J., Di Santo J.P.: IL-7 and IL-15 independently programthe differentiation of intestinal CD3−NKp46+ cell subsets from Id2-dependentprecursors. J. Exp. Med., 2010; 207: 273-280
  Google Scholar
• 44. Satoh-Takayama N., Vosshenrich C.A., Lesjean-Pottier S., Sawa S.,Lochner M., Rattis F., Mention J.J., Thiam K., Cerf-Bensussan N., MandelboimO., Eberl G., Di Santo J.P.: Microbial flora drives interleukin 22production in intestinal NKp46+ cells that provide innate mucosal immunedefense. Immunity, 2008; 29: 958-970
  Google Scholar
• 45. Sawa S., Cherrier M., Lochner M., Satoh-Takayama N., Jörg FehlingH., Langa F., Di Santo J.P., Eberl G.: Lineage relationship analysis ofRORγt+ innate lymphoid cells. Science, 2010; 330: 665-669
  Google Scholar
• 46. Scandella E., Bolinger B., Lattmann E., Miller S., Favre S., LittmanD.R., Finke D., Luther S.A., Junt T., Ludewig B.: Restoration of lymphoidorgan integrity through the interaction of lymphoid tissue-inducercells with stroma of the T cell zone. Nat. Immunol., 2008; 9: 667-675
  Google Scholar
• 47. Schmutz S., Bosco N., Chappaz S., Boyman O., Acha-Orbea H., CeredigR., Rolink A.G., Finke D.: Cutting edge: IL-7 regulates the peripheralpool of adult RORγ+ lymphoid tissue inducer cells. J. Immunol., 2009;183: 2217-2221
  Google Scholar
• 48. Spits H., Artis D., Colonna M., Diefenbach A., Di Santo J.P., Eberl G.,Koyasu S., Locksley R.M., McKenzie A.N., Mebius R.E., Powrie F., VivierE.: Innate lymphoid cells – a proposal for uniform nomenclature. Nat.Rev. Immunol., 2013; 13: 145-149
  Google Scholar
• 49. Spits H., Cupedo T.: Innate lymphoid cells: emerging insights indevelopment, lineage relationships and function. Annu. Rev. Immunol.,2012; 30: 647-675
  Google Scholar
• 50. Spits H., Santo J.P.: The expanding family of innate lymphoid cells:regulators and effectors of immunity and tissue remodeling. NatureImmunol., 2011; 11: 21-27
  Google Scholar
• 51. Sun Z., Unutmaz D., Zou R.U., Sunshine M.J., Pierani A., Brenner–Morton S., Mebius R.E., Littman D.R.: Requirement for RORγ in thymocytesurvival and lymphoid organ development. Science, 2000; 288:2369-2373
  Google Scholar
• 52. Trinchieri G.: Biology of natural killer cells. Adv. Immunol., 1989;47: 187-376
  Google Scholar
• 53. Tsuji M., Suzuki K., Kitamura H., Maruya M., Kinoshita K., IvanovI.I., Itoh K., Littman D.R., Fagarasan S.: Requirement for lymphoid tissue-inducercells in isolated follicle formation and T cell-independentimmunoglobulin A generation in the gut. Immunity, 2008; 29: 261-271
  Google Scholar
• 54. van de Pavert S.A., Mebius R.E.: New insights into the developmentof lymphoid tissues. Nat. Rev. Immunol., 2010; 10: 664-674
  Google Scholar
• 55. Vosshenrich C.A., Di Santo J.P.: Developmental programming ofnatural killer and innate lymphoid cells. Curr. Opin. Immunol., 2013;25: 130-138
  Google Scholar
• 56. Vosshenrich C.A., García-Ojeda M.E., Samson-Villéger S.I., PasqualettoV., Enault L., Richard-Le Goff O., Corcuff E., Guy-Grand D., RochaB., Cumano A., Rogge L., Ezine S., Di Santo J.P.: A thymic pathway ofmouse natural killer cell development characterized by expression ofGATA-3 and CD127. Nat. Immunol., 2006; 7: 1217-1224
  Google Scholar
• 57. Walker J.A., Barlow J.L., McKenzie A.N.: Innate lymphoid cells – howdid we miss them?. Nat. Rev. Immunol., 2013; 13: 75-87
  Google Scholar
• 58. Walker J.A., McKenzie A.N.: Development and function of group 2innate lymphoid cells. Curr. Opin. Immunol., 2013; 25: 148-155
  Google Scholar
• 59. Wolk K., Witte E., Witte K., Warszawska K., Sabat R.: Biology of interleukin-22.Semin. Immunopathol., 2010; 32: 17-31
  Google Scholar
• 60. Yokota Y., Mansouri A., Mori S., Sugawara S., Adachi S., NishikawaS., Gruss P.: Development of peripheral lymphoid organs and naturalkiller cells depends on the helix-loop-helix inhibitor Id2. Nature, 1999;397: 702-706
  Google Scholar
• 61. Zheng Y., Valdez P.A., Danilenko D.M., Hu Y., Sa S.M., Gong Q., AbbasA.R., Modrusan Z., Ghilardi N., de Sauvage F.J., Ouyang W.: Interleukin-22mediates early host defense against attaching and effacing bacterialpathogens. Nat. Med., 2008; 14: 282-289
  Google Scholar

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