Citation: de Freitas, F.A.; Levy, D.;
Reichert, C.O.; Cunha-Neto, E.; Kalil,
J.; Bydlowski, S.P. Effects of
Oxysterols on Immune Cells and
Related Diseases. Cells 2022, 11, 1251.
https://doi.org/10.3390/cells11081251
Academic Editors: John J. Mackrill,
Gérard Lizard and Tim Willinger
Received: 13 March 2022
Accepted: 5 April 2022
Published: 7 April 2022
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cells
Review
Effects of Oxysterols on Immune Cells and Related Diseases
Fábio Alessandro de Freitas
1
,Débora Levy
1
, Cadiele Oliana Reichert
1
, Edecio Cunha-Neto
2,3
,
Jorge Kalil
3,4
and Sérgio Paulo Bydlowski
1,5,
*
1
Lipids, Oxidation and Cell Biology Team, Laboratory of Immunology (LIM19), Heart Institute (InCor),
Faculdade de Medicina, Universidade de São Paulo, Sao Paulo 05403-900, SP, Brazil;
fabio.alessandro@usp.br (F.A.d.F.); d.levy@hc.fm.usp.br (D.L.); kadielli@hotmail.com (C.O.R.)
2
Laboratory of Clinical Immunology and Allergy (LIM60), Heart Institute (InCor), Faculdade de Medicina,
Universidade de São Paulo, Sao Paulo 05403-900, SP, Brazil; edecunha@usp.br
3
National Institute of Science and Technology for Investigation in Immunology-III/INCT,
Sao Paulo 05403-000, SP, Brazil; jkalil@usp.br
4
Laboratory of Immunology (LIM19), Heart Institute (InCor), Faculdade de Medicina, Universidade de São
Paulo, Sao Paulo 05403-900, SP, Brazil
5
National Institute of Science and Technology in Regenerative Medicine (INCT-Regenera), CNPq,
Rio de Janeiro 21941-902, RJ, Brazil
* Correspondence: spbydlow@usp.br
Abstract: Oxysterols are the products of cholesterol oxidation. They have a wide range of effects
on several cells, organs, and systems in the body. Oxysterols also have an influence on the physi-
ology of the immune system, from immune cell maturation and migration to innate and humoral
immune responses. In this regard, oxysterols have been involved in several diseases that have an
immune component, from autoimmune and neurodegenerative diseases to inflammatory diseases,
atherosclerosis, and cancer. Here, we review data on the participation of oxysterols, mainly 25-
hydroxycholesterol and 7α,25-dihydroxycholesterol, in the immune system and related diseases. The
effects of these oxysterols and main oxysterol receptors, LXR and EBI2, in cells of the immune system
(B cells, T cells, macrophages, dendritic cells, oligodendrocytes, and astrocytes), and in immune-
related diseases, such as neurodegenerative diseases, intestinal diseases, cancer, respiratory diseases,
and atherosclerosis, are discussed.
Keywords: oxysterols; 25-hydroxycholesterol; 7α,25-dihydroxycholesterol; immune cells; immune
diseases; EBI2; LXR
1. Introduction
Cholesterol is a vital component of cellular membranes [1,2] comprising about 20%
of lipids present in plasma membrane [3,4]. Consequently, cholesterol plays a key role
in maintaining the membrane integrity and fluidity, as well as having an impact on
cellular physiology [3,4].
Oxysterols are oxidized derivatives of cholesterol [5–8], being intermediate compounds
in the biosynthesis of bile acids, steroid hormones, and 1,25-dihydroxyvitamin D3 [5,9,10].
Oxysterols can be formed either enzymatically, by the action of some members of the CYP
(cytochrome P450) family, or non-enzymatically, by the action of ROS (Figure 1)[3,9,10].
Oxysterols present in the diet may contribute to the total pool of oxysterols in the body [9,10].
Oxysterols can also be classified into those synthesized directly from cholesterol, the
primary oxysterols, which are formed by side-chain changes (such as 24S-, 25-, (25R)-26 and
27-hydroxycholesterols), and by ring changes (which includes 7α-hydroxycholesterol and
7β-hydroxycholesterol); and those derived from primary oxysterols, the secondary oxysterols,
such as 7α,25-dihydroxycholesterol (Figure 1) and 7α,(25R)-26-dihydroxycholesterol, which
are generated from 25-hydroxycholesterol and (25R)-26-hydroxycholesterol, respectively [11].
Cells 2022, 11, 1251. https://doi.org/10.3390/cells11081251 https://www.mdpi.com/journal/cells