IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin
Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4’s role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent repo...
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doaj-e1689f79c3bd4dcd8d085bd3b1ca59c12020-11-24T22:57:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-06-01910.3389/fimmu.2018.01211354798IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and SkinMelanie Sarah ProutRyan L. KyleFranca RoncheseGraham Le GrosAlthough IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4’s role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis (Nb) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues. In the lymph node, a CXCR5+PD-1+ T follicular helper (Tfh) and a CXCR5loPD-1lo Th2 subset could be detected that expressed only IL-4AC but no IL-13DR. The number of IL-4AC+ Tfh cells was not affected by IL-4 deficiency whereas the number of IL-4AC+ Th2 cells was significantly reduced. In the non-lymphoid dermal or lung tissues of allergen primed or Nb-infected mice, three strikingly distinct T cell subsets could be detected that were IL-4AC, or IL-4AC/IL-13DR, or IL-13DR CD4. The IL-4- and IL-4/IL-13-expressing subsets were significantly reduced in IL-4-deficient mice, while the numbers of IL-13-expressing CD4 T cells were not affected by IL-4 deficiency indicating that other factors can play a role in directing the development of this Th2 subtype. Taken together, these data indicate that the appearance of IL-4-expressing Tfh cells in the lymph node is not dependent on IL-4 while the appearance of IL-4-expressing Th2 subsets in the lymph node and IL-4, IL-4/IL-13-expressing Th2 subsets in skin and lung tissues of antigen primed mice is significantly IL-4 dependent.https://www.frontiersin.org/article/10.3389/fimmu.2018.01211/fullTh2IL-4IL-13skinlymph nodelung |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Melanie Sarah Prout Ryan L. Kyle Franca Ronchese Graham Le Gros |
spellingShingle |
Melanie Sarah Prout Ryan L. Kyle Franca Ronchese Graham Le Gros IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin Frontiers in Immunology Th2 IL-4 IL-13 skin lymph node lung |
author_facet |
Melanie Sarah Prout Ryan L. Kyle Franca Ronchese Graham Le Gros |
author_sort |
Melanie Sarah Prout |
title |
IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin |
title_short |
IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin |
title_full |
IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin |
title_fullStr |
IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin |
title_full_unstemmed |
IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin |
title_sort |
il-4 is a key requirement for il-4- and il-4/il-13-expressing cd4 th2 subsets in lung and skin |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2018-06-01 |
description |
Although IL-4 is long associated with CD4 Th2 immune responses, its role in Th2 subset development in non-lymphoid tissues is less clear. We sought to better define IL-4’s role in CD4 Th2 responses by using transgenic mice that express a dual IL-4 AmCyan/IL-13 DsRed (IL-4AC/IL-13DR) fluorescent reporter on an IL-4-sufficient or IL-4-deficient background. Using primary Th2 immune response models against house dust mite or Nippostrongylus brasiliensis (Nb) allergens, we examined the requirement for IL-4 by each of the defined Th2 subsets in the antigen draining lymph node, skin, and lung tissues. In the lymph node, a CXCR5+PD-1+ T follicular helper (Tfh) and a CXCR5loPD-1lo Th2 subset could be detected that expressed only IL-4AC but no IL-13DR. The number of IL-4AC+ Tfh cells was not affected by IL-4 deficiency whereas the number of IL-4AC+ Th2 cells was significantly reduced. In the non-lymphoid dermal or lung tissues of allergen primed or Nb-infected mice, three strikingly distinct T cell subsets could be detected that were IL-4AC, or IL-4AC/IL-13DR, or IL-13DR CD4. The IL-4- and IL-4/IL-13-expressing subsets were significantly reduced in IL-4-deficient mice, while the numbers of IL-13-expressing CD4 T cells were not affected by IL-4 deficiency indicating that other factors can play a role in directing the development of this Th2 subtype. Taken together, these data indicate that the appearance of IL-4-expressing Tfh cells in the lymph node is not dependent on IL-4 while the appearance of IL-4-expressing Th2 subsets in the lymph node and IL-4, IL-4/IL-13-expressing Th2 subsets in skin and lung tissues of antigen primed mice is significantly IL-4 dependent. |
topic |
Th2 IL-4 IL-13 skin lymph node lung |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2018.01211/full |
work_keys_str_mv |
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