RATIONALE: The liver-specific natural killer (NK) cell population is critical for local innate immune responses, but the mechanisms that lead to their selective homing and the definition of their functionally relevance remain enigmatic. OBJECTIVES: We took advantage of the availability of healthy human liver to rigorously define the mechanisms regulating the homing of NK cells to liver and the repertoire of receptors that distinguish liver-resident NK (lr-NK) cells from circulating counterparts. FINDINGS: Nearly 50% of the entire liver NK cell population is composed of functionally relevant CD56(bright) lr-NK cells that localize within hepatic sinusoids. CD56(bright) lr-NK cells express CD69, CCR5 and CXCR6 and this unique repertoire of chemokine receptors is functionally critical as it determines selective migration in response to the chemotactic stimuli exerted by CCL3, CCL5 and CXCL16. Here, we also show that hepatic sinusoids express CCL3(pos) Kupffer cells, CXCL16(pos) endothelial cells and CCL5(pos) T and NK lymphocytes. The selective presence of these chemokines in sinusoidal spaces creates a unique tissue niche for lr-CD56(bright) NK cells that constitutively express CCR5 and CXCR6. CD56(bright) lr-NK cells co-exist with CD56(dim) conventional NK (c-NK) cells that are, interestingly, transcriptionally and phenotypically similar to their peripheral circulating counterparts. Indeed, CD56(dim) c-NK cells lack expression of CD69, CCR5, and CXCR6 but express selectins, integrins and CX3CR1.

Human liver-resident CD56bright/CD16neg NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways / K. Hudspeth, M. Donadon, M. Cimino, E. Pontarini, P. Tentorio, M. Preti, M. Hong, A. Bertoletti, S. Bicciato, P. Invernizzi, E. Lugli, G. Torzilli, M. Eric Gershwin, D. Mavilio. - In: JOURNAL OF AUTOIMMUNITY. - ISSN 0896-8411. - 66(2016 Dec), pp. 40-50.

Human liver-resident CD56bright/CD16neg NK cells are retained within hepatic sinusoids via the engagement of CCR5 and CXCR6 pathways

K. Hudspeth
Primo
;
M. Donadon
Secondo
;
M. Cimino;P. Invernizzi;G. Torzilli;D. Mavilio
2016

Abstract

RATIONALE: The liver-specific natural killer (NK) cell population is critical for local innate immune responses, but the mechanisms that lead to their selective homing and the definition of their functionally relevance remain enigmatic. OBJECTIVES: We took advantage of the availability of healthy human liver to rigorously define the mechanisms regulating the homing of NK cells to liver and the repertoire of receptors that distinguish liver-resident NK (lr-NK) cells from circulating counterparts. FINDINGS: Nearly 50% of the entire liver NK cell population is composed of functionally relevant CD56(bright) lr-NK cells that localize within hepatic sinusoids. CD56(bright) lr-NK cells express CD69, CCR5 and CXCR6 and this unique repertoire of chemokine receptors is functionally critical as it determines selective migration in response to the chemotactic stimuli exerted by CCL3, CCL5 and CXCL16. Here, we also show that hepatic sinusoids express CCL3(pos) Kupffer cells, CXCL16(pos) endothelial cells and CCL5(pos) T and NK lymphocytes. The selective presence of these chemokines in sinusoidal spaces creates a unique tissue niche for lr-CD56(bright) NK cells that constitutively express CCR5 and CXCR6. CD56(bright) lr-NK cells co-exist with CD56(dim) conventional NK (c-NK) cells that are, interestingly, transcriptionally and phenotypically similar to their peripheral circulating counterparts. Indeed, CD56(dim) c-NK cells lack expression of CD69, CCR5, and CXCR6 but express selectins, integrins and CX3CR1.
Cherokees Chemokine receptors; Homing of hepatic NK cells; Liver immunology; Immunology; Immunology and Allergy
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
Settore MED/04 - Patologia Generale
Settore MED/06 - Oncologia Medica
Settore MED/16 - Reumatologia
30-ago-2015
Article (author)
File in questo prodotto:
File Dimensione Formato  
1-s2.0-S0896841115300299-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.69 MB
Formato Adobe PDF
1.69 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
1-s2.0-S0896841115300299-main.pdf

accesso riservato

Tipologia: Publisher's version/PDF
Dimensione 1.63 MB
Formato Adobe PDF
1.63 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/343536
Citazioni
  • ???jsp.display-item.citation.pmc??? 117
  • Scopus 166
  • ???jsp.display-item.citation.isi??? 162
social impact