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...

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Published inFrontiers in immunology Vol. 9; p. 1211
Main Authors Prout, Melanie Sarah, Kyle, Ryan L, Ronchese, Franca, Le Gros, Graham
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 01.06.2018
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Abstract 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 ( ) 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 CXCR5 PD-1 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 -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.
AbstractList 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.
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 CXCR5 lo PD-1 lo 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.
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 ( ) 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 CXCR5 PD-1 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 -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.
Author Kyle, Ryan L
Ronchese, Franca
Le Gros, Graham
Prout, Melanie Sarah
AuthorAffiliation Malaghan Institute of Medical Research , Wellington , New Zealand
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Keywords lung
non-lymphoid tissues
lymph node
IL-4
skin
IL-13
Th2
Language English
License This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Reviewed by: Carla Rothlin, Yale University, United States; Yisong Wan, University of North Carolina at Chapel Hill, United States
Present address: Ryan L. Kyle, Department of Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany
Specialty section: This article was submitted to T Cell Biology, a section of the journal Frontiers in Immunology
Edited by: Jinfang Zhu, National Institute of Allergy and Infectious Diseases (NIAID), United States
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Snippet 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...
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StartPage 1211
SubjectTerms IL-13
IL-4
Immunology
lung
lymph node
skin
Th2
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Title IL-4 Is a Key Requirement for IL-4- and IL-4/IL-13-Expressing CD4 Th2 Subsets in Lung and Skin
URI https://www.ncbi.nlm.nih.gov/pubmed/29910811
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https://pubmed.ncbi.nlm.nih.gov/PMC5992292
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Volume 9
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