nuocyte

The nuocyte is a cell of the innate immune system that plays an important role in type 2 immune responses that are induced in response to helminth worm infection or in conditions such as asthma and atopic disease.{{cite journal|last=Neill|first=DR |author2=Wong, SH |author3=Bellosi, A |author4=Flynn, RJ |author5=Daly, M |author6=Langford, TK |author7=Bucks, C |author8=Kane, CM |author9=Fallon, PG |author10=Pannell, R |author11=Jolin, HE |author12=McKenzie, AN|authorlink12=Andrew N. J. McKenzie|title=Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.|journal=Nature|year=2010|volume=464|issue=7293|pages=1367–70|pmid=20200518|doi=10.1038/nature08900|pmc=2862165|bibcode=2010Natur.464.1367N }} Nuocytes are amongst the first cells activated in type 2 immune responses and are thought to play important roles in activating and recruiting other cells types through their production of type 2 cytokines interleukin 4, 5 and 13. Nuocytes have been observed to proliferate in the presence of interleukin 7 (IL-7) in vitro.{{cite journal|last1=Mirchandani|first1=A|last2=Salmond|first2=R|last3=Liew|first3=F|title=Interleukin-33 and the function of innate lymphoid cells|journal=Trends in Immunology|date=2012|volume=33|issue=8|pages=389–396|doi=10.1016/j.it.2012.04.005|pmid=22609147}} Nuocytes contribute to the expulsion of helminth worms and to the pathology of colitis{{cite journal|last=Camelo|first=A |author2=Barlow, JL |author3=Drynan, LF |author4=Neill, DR |author5=Ballantyne, SJ |author6=Wong, SH |author7=Pannell, R |author8=Gao, W |author9=Wrigley, K |author10=Sprenkle, J |author11=McKenzie, AN|title=Blocking IL-25 signalling protects against gut inflammation in a type-2 model of colitis by suppressing nuocyte and NKT derived IL-13.|journal=Journal of Gastroenterology|date=2012-04-27|pmid=22539101|doi=10.1007/s00535-012-0591-2|volume=47|issue=11|pmc=3501170|pages=1198–211}} and allergic airways disease.{{cite journal|last=Barlow|first=JL|author2=Bellosi, A |author3=Hardman, CS |author4=Drynan, LF |author5=Wong, SH |author6=Cruickshank, JP |author7= McKenzie, AN |title=Innate IL-13-producing nuocytes arise during allergic lung inflammation and contribute to airways hyperreactivity.|journal=The Journal of Allergy and Clinical Immunology|date=Jan 2012|volume=129|issue=1|pages=191–8.e1–4|pmid=22079492|doi=10.1016/j.jaci.2011.09.041}}

The nuocyte was identified at the same time as several other immune cells that play similar roles in type 2 immunity. These include Natural Helper Cells (NHCs),{{cite journal|last=Moro|first=K|author2=Yamada, T |author3=Tanabe, M |author4=Takeuchi, T |author5=Ikawa, T |author6=Kawamoto, H |author7=Furusawa, J |author8=Ohtani, M |author9=Fujii, H |author10= Koyasu, S |title=Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells.|journal=Nature|date=2010-01-28|volume=463|issue=7280|pages=540–4|pmid=20023630|doi=10.1038/nature08636|s2cid=4420895}} Innate Helper 2 (Ih2) cells {{cite journal|last=Price|first=AE|author2=Liang, HE |author3=Sullivan, BM |author4=Reinhardt, RL |author5=Eisley, CJ |author6=Erle, DJ |author7= Locksley, RM |title=Systemically dispersed innate IL-13-expressing cells in type 2 immunity.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=2010-06-22|volume=107|issue=25|pages=11489–94|pmid=20534524|doi=10.1073/pnas.1003988107|pmc=2895098|bibcode=2010PNAS..10711489P|doi-access=free}} and multi-potent progenitor (MPP) type 2 cells.{{cite journal|last=Saenz|first=SA |author2=Siracusa, MC |author3=Perrigoue, JG |author4=Spencer, SP |author5=Urban JF Jr |author6=Tocker, JE |author7=Budelsky, AL |author8=Kleinschek, MA |author9=Kastelein, RA |author10=Kambayashi, T |author11=Bhandoola, A |author12=Artis, D |title=IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses.|journal=Nature|date=2010-04-29|volume=464|issue=7293|pages=1362–6|pmid=20200520|doi=10.1038/nature08901|pmc=2861732|bibcode=2010Natur.464.1362S }} The exact relationship between these cell types remains contentious {{cite journal|last=Neill|first=DR|author2=McKenzie, AN |title=Nuocytes and beyond: new insights into helminth expulsion.|journal=Trends in Parasitology|date=May 2011|volume=27|issue=5|pages=214–21|pmid=21292555|doi=10.1016/j.pt.2011.01.001}}{{cite journal|last=Saenz|first=SA|author2=Noti, M |author3=Artis, D |title=Innate immune cell populations function as initiators and effectors in Th2 cytokine responses.|journal=Trends in Immunology|date=Nov 2010|volume=31|issue=11|pages=407–13|pmid=20951092|doi=10.1016/j.it.2010.09.001}} but all share a type-2-inducing phenotype. MPP type 2 cells appear to differ from the other populations in that they have a myeloid, rather than lymphoid, origin.

Nuocytes have been shown to have a lymphoid origin and a developmental pathway that is dependent upon the transcription factor RORα and Notch signalling.{{cite journal|last=Wong|first=SH |author2=Walker, JA |author3=Jolin, HE |author4=Drynan, LF |author5=Hams, E |author6=Camelo, A |author7=Barlow, JL |author8=Neill, DR |author9=Panova, V |author10=Koch, U |author11=Radtke, F |author12=Hardman, CS |author13=Hwang, YY |author14=Fallon, PG |author15=McKenzie, AN |title=Transcription factor RORα is critical for nuocyte development.|journal=Nature Immunology|date=2012-01-22|volume=13|issue=3|pages=229–36|pmid=22267218|doi=10.1038/ni.2208|pmc=3343633}} Pro-T cell progenitors retain nuocyte developmental potential but, unlike T cells, the thymus is dispensable for their development.