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Vitamins A and D have antagonistic effects on expression of effector cytokines and gut‐homing integrin in human innate lymphoid cells
Author(s) -
Ruiter B.,
Patil S. U.,
Shreffler W. G.
Publication year - 2015
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12568
Subject(s) - innate lymphoid cell , biology , cytokine , immunology , homing (biology) , retinoic acid , immune system , microbiology and biotechnology , innate immune system , cell culture , ecology , genetics
Summary Background Retinoic acid ( RA ), the main biologically active metabolite of vitamin A, is known to promote gut homing of lymphocytes, as well as various regulatory and effector immune responses. In contrast, the active form of vitamin D, 1,25‐dihydroxyvitamin D 3 (1,25D3), is predominantly immunosuppressive. Little is known about the direct effects of these vitamins on the recently identified innate lymphoid cells ( ILC s). Objective We sought to characterize the effects of RA and 1,25D3 on human ILC s. Methods Peripheral blood mononuclear cells were isolated from 27 non‐selected blood donor buffy coats, and ILC s were sorted by FACS . ILC 1, ILC 2, and ILC 3 cells were cultured for 5 days with RA , 1,25D3, and various cytokines known to activate ILC s ( IL ‐2, IL ‐7, IL ‐12, thymic stromal lymphopoietin ( TSLP ), IL ‐25, and IL ‐33). Cytokines produced by ILC s were measured in culture supernatants, and surface receptor expression was analysed by flow cytometry. Results Retinoic acid acted synergistically with IL ‐2 and other activating cytokines to induce expression of the gut‐homing integrin α4β7 in ILC s, as well as production of IL ‐5 and IL ‐13 in ILC 2 cells, and IFN ‐γ in ILC 1 and ILC 3 cells. Expression of integrin α4β7 and cytokine production in ILC s stimulated with RA + IL ‐2 was increased at least fourfold as compared to ILC s cultured with RA or IL ‐2 alone. In contrast, RA completely inhibited the IL ‐2‐induced expression of cutaneous lymphocyte antigen ( CLA ) in ILC s. Moreover, addition of 1,25D3 to ILC s cultured with RA + IL ‐2 inhibited cytokine production and expression of integrin α4β7 by at least 30%. Conclusions Retinoic acid and 1,25D3 have antagonistic effects on the expression of effector cytokines and gut‐homing integrin by human ILC s. The balance between these vitamins may be an important factor in the functioning of ILC s and the diseases in which ILC s are implicated, such as allergic inflammation.